Information

15.8E: Drugs and the Nervous System - Biology

15.8E: Drugs and the Nervous System - Biology


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

The activity of the nervous system is mediated by many kinds of interneurons releasing one or another neurotransmitter such as

  • noradrenaline
  • gamma aminobutyric acid (GABA)
  • dopamine
  • glutamate (Glu)
  • acetylcholine (ACh)
  • serotonin

Presynaptic neurons synthesize and package their neurotransmitter in vesicles for release (by exocytosis) at the synapse. They often have "reuptake" transporters that reclaim the transmitter back into the cell when it has done its job. Postsynaptic neurons display receptors to which the neurotransmitter binds. All of this machinery provides many targets for alteration by exogenous chemicals; that is, psychoactive chemicals introduced into the body. These drugs fall into several distinct families.

Stimulants

The most widely used stimulants are

  • caffeine (in coffee, tea, and cola beverages)
  • nicotine (in cigarettes)
  • amphetamines
  • cocaine

All of these drugs mimic the stimulation provided by the sympathetic nervous system.

Nicotine binds to a subset of acetylcholine (ACh) receptors. ACh is a neurotransmitter at synapses early in the pathways of sympathetic stimulation. Although a weak drug in one sense, nicotine is strongly addictive. The use of e-cigarettes, chewing gum and skin patches containing nicotine is designed to satisfy the craving for nicotine while avoiding the serious health effects of other ingredients in cigarette smoke.

Amphetamines and cocaine bind to — thus blocking — transporters used for the reuptake of dopamine (and noradrenaline) into presynaptic neurons. This causes the level of dopamine to rise in the synapses. High levels of dopamine in an area of the brain called the nucleus accumbens appear to mediate the pleasurable effects associated with these (as well as other) psychoactive drugs.

Table 1: Some amphetamines
Generic nameTrade name
dextroamphetamine sulfateDexedrine
methylphenidateRitalin
pemolineCylert
mixture of 4 amphetaminesAdderall

The chief medical uses for amphetamines and amphetamine-like drugs are to help people lose weight (because they suppress appetite) and to help children with attention deficit/hyperactivity disorder (ADHD) to perform better in school. At first glance, this second use seems counterproductive. This controversial procedure seems to work by increasing the alertness of the child so that it can focus its energies more effectively on the tasks in front of it.

Fen-Phen

Fen-Phen refers to a mixture of two amphetamine-like drugs fenfluramine and phentermine that were prescribed for losing weight. Because of reports of occasional very serious side effects, the mixture is no longer available and fenfluramine has been removed from the U.S. market.

Cocaine

Cocaine has been used for thousands of years by certain tribes in the Andes of South America. Cocaine and some of its relatives have legitimate medical uses as local anesthetics (e.g., lidocaine). However, the widespread recreational use of cocaine has created serious social problems. In order to achieve its effects, cocaine must cross the so-called blood-brain barrier. If antibodies are bound to the cocaine molecule, it cannot cross. This has raised the possibility of immunizing people against cocaine. It works in mice.

Sedatives

Sedatives induce sleep. They include

  • ethanol (beverage alcohol)
  • barbiturates, such as
    • phenobarbital
    • secobarbital (Seconal®)
  • meprobamate (Miltown®, Equanil®)

Ethanol

Ethyl alcohol (ethanol) is, by a wide margin, the most widely used drug in most of the world. Its popularity comes not from its sedative effect but from the sense of well-being that it induces at low doses. Perhaps low doses sedate those parts of the brain involved with, for example, tension and anxiety and in this way produce a sense of euphoria. However, higher doses depress brain centers involved in such important functions as pain sensation, coordination, and balance. At sufficiently high doses, the reticular formation can be depressed enough to cause loss of consciousness.

Ethanol increases the release of the neurotransmitter GABA activating GABAA receptors and directly inhibits NMDA receptors.

Barbiturates

Barbiturates are often prescribed as sleeping pills and also to prevent seizures. Barbiturates mimic some of the action of ethanol, particularly in their ability to depress the reticular formation (thus promoting sleep) and, in high doses, the medulla oblongata (thus stopping breathing).

Barbiturates bind to a subset of GABA receptors designated GABAA receptors. These are ligand-gated channels that enhance the flow of chloride ions (Cl) into the postsynaptic neuron, thus increasing its resting potential and making it less likely to fire. By binding to the GABAA receptor, barbiturates (and perhaps ethanol) increase the natural inhibitory effect of GABA synapses. Barbiturates and alcohol act additively — the combination producing a depression greater than either one alone. The combination is a frequent cause of suicide, both accidental and planned.

Meprobamate

Meprobamate is prescribed as a tranquilizer, but its action is quite different from the tranquilizers discussed below. Its molecular activity is like that of other sedatives and in combination with them can produce a lethal overdose. All sedatives produce two related physiological effects:

  • tolerance — the necessity for a steadily-increasing dose to achieve the same physiological and psychological effects
  • physical dependence — withdrawal of the drug precipitates unpleasant physical and psychological symptoms.

These traits are also shared with nicotine, opioids, and other psychoactive drugs.

Local Anesthetics

These chemical relatives of cocaine act by blocking the voltage-gated Na+ channels of sensory neurons preventing them from generating action potentials. They are injected or applied topically and block transmission not only in pain-conducting neurons but in others as well (causing general numbness).

Examples:

  • lidocaine (Xylocaine®)
  • procaine (Novocaine®)

Inhaled Anesthetics

Most of these are volatile hydrocarbons or ethers. Diethyl ether and chloroform are seldom used today, having been replaced by safer alternatives such as isofluorane, a fluorinated ether. Some, like isofluorane, bind to inhibitory GABA receptors) in the brain hyperpolarizing, and thus decreasing the sensitivity of, postsynaptic neurons. Others, like ketamine, block the activity of excitatory glutamate receptors.

Other Hydrocarbons

1,4-Butanediol is a common solvent. When ingested, it is converted into γ-hydroxybutyrate, an increasingly-popular (and illegal) "club drug". γ-Hydroxybutyrate acts on GABAB receptors. Conversion of 1,4-butanediol to γ-hydroxybutyrate requires the enzyme alcohol dehydrogenase, the same enzyme used to metabolize ethanol. Ingesting both ethanol and 1,4-butanediol delays the effects of the latter.

Opioids

These are substances isolated from the opium poppy or synthetic relatives. (They are also called opiates.)
Examples:

  • morphine
  • codeine
  • heroin
  • fentanyl (a synthetic that is ~80 times more potent than morphine)
  • methadone
  • oxycodone

Opioids depress nerve transmission in sensory pathways of the spinal cord and brain that signal pain. This explains why opioids are such effective pain killers. Opioids also inhibit brain centers controlling coughing, breathing, and intestinal motility. Both morphine and codeine are used as pain killers, and codeine is also used in cough medicine. Opioids are exceedingly addictive, quickly producing tolerance and dependence. Although heroin is even more effective as a painkiller than morphine and codeine, it is so highly addictive that its use is illegal. Methadone is a synthetic opioid that is used to break addiction to heroin (and replace it with addiction to methadone).

Opioids bind to so-called mu (µ) receptors . These G-protein-coupled receptors are located on the subsynaptic membrane of neurons involved in the transmission of pain signals. Their natural ligands are two pentapeptides (containing five amino acids):

  • Met-enkephalin (Tyr-Gly-Gly-Phe-Met-COO-)
  • Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu-COO-)

Release of enkephalins suppresses the transmission of pain signals. Little is to be gained by having the perception of pain increase indefinitely in proportion to the amount of damage done to the body. Beyond a certain point, it makes sense to have a system that decreases its own sensitivity in the face of massive, intractable pain.

By binding to mu (µ) receptors, opioids like morphine enhance the pain-killing effects of enkephalin neurons. Opioid tolerance can be explained, at least in part, as a homeostatic response that reduces the sensitivity of the system to compensate for continued exposure to high levels of morphine or heroin. When the drug is stopped, the system is no longer as sensitive to the soothing effects of the enkephalin neurons and the pain of withdrawal is produced.

Mu (µ) receptors are also found on the cells in the medulla oblongata that regulate breathing. This accounts for the suppressive effect opioids have on breathing.

Opioid antagonists

Opioid antagonists such as naloxone (Narcan®) and naltrexone (ReVia®) bind to µ receptors but instead of activating them, they prevent the binding of the opioids themselves. In fact, if the receptors are already occupied by, for example, heroin molecules, naloxone will push the heroin molecules off and quickly rescue the patient from a drug overdose. Naltrexone is used to help recovering heroin addicts stay drug-free.

Antipsychotics

Antipsychotics (also called "neuroleptics") are used to treat schizophrenia, a common and devastating mental disease. They act by binding to one class of receptors for the neurotransmitter dopamine. There are two groups currently in use:

  • "Typical" antipsychotics (sometimes referred to as "major tranquilizers"). Examples:
    • chlorpromazine (Thorazine®)
    • haloperidol (Haldol®)
  • "Atypical" antipsychotics (also referred to as "second generation" antipsychotics). Examples:
    • risperidone (Risperdal®)
    • olanzapine (Zyprexa®)
    • quetiapine (Seroquel®)

Tranquilizers

Tranquilizers act like sedatives in reducing anxiety and tensions. Most belong to a group called benzodiazepines and include such commonly-prescribed drugs as Xanax® and Klonopin®. The benzodiazepines act on interneurons that use the inhibitory neurotransmitter GABA. By binding to GABAA receptors on the postsynaptic membrane, they enhance the action of GABA at the synapse.This is the same receptor to which barbiturates (and perhaps ethanol) bind. Thus although benzodiazepines seem safe enough when used alone, combining them with ethanol or barbiturates can be (and often has been) lethal.

Antidepressants

Antidepressants fall into four chemical categories (of which we shall examine three). Most share a common property: they increase the amount of serotonin at synapses that use it as a neurotransmitter.

Monoamine oxidase inhibitors (MAOIs)

These drugs act on a mitochondrial enzyme that breaks down monoamines such as noradrenaline and serotonin. By inhibiting the enzyme in presynaptic serotonin-releasing neurons, more noradrenaline and serotonin is deposited in the synapse. Some examples: Parnate®, Nardil®, Marplan®. For several reasons, MAO inhibitors are not used much anymore.

Tricyclic antidepressants (TCAs)

These drugs block the reuptake of noradrenaline, dopamine, and serotonin causing an increase in the level of these neurotransmitters in the synapse.

Examples:

Generic nameTrade name
imipramineTofranil®
clomiprimineAnafranil®
amitriptylineElavil®

Although tricyclics are still prescribed for pain relief, their role as antidepressants has largely been taken over by the serotonin reuptake inhibitors (SRIs).

Selective serotonin reuptake inhibitors (SSRIs)

These drugs inhibit the reuptake of serotonin but not of noradrenaline.

Examples:

Generic nameTrade name
fluoxetineProzac®
paroxetinePaxil®
sertralineZoloft®

Although all these drugs quickly increase the amount of serotonin in the brain, there is more to the story than that. Unlike most psychoactive drugs, antidepressants do not relieve the symptoms of depression until a week or more after dosing begins. During this period, the number of serotonin receptors on the postsynaptic membranes decreases. How this translates into relief of symptoms is not yet understood.

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Because they act on the reuptake of both serotonin and noradrenaline (norepinephrine), this category of antidepressants is also known as dual reuptake inhibitors.

Examples: venlafaxine (Effexor®) and duloxetine (Cymbalta®).

Bupropion

Bupropion (Wellbutrin®) is a novel drug that blocks the reuptake of noradrenaline and dopamine. Although it does not interfere with the uptake of serotonin, it also appears to be an effective antidepressant.

Atomoxetine

This drug (Strattera®) selectively interferes with the reuptake of noradrenaline. It is used in children with attention deficit/hyperactivity disorder (ADHD).

Psychedelics

Psychedelic drugs distort sensory perceptions, especially sight and sound. Some such as mescaline, psilocybin and dimethyltryptamine (DMT) are natural plant products.

The photograph shows the peyote cactus in flower. The cactus head contains several psychedelic chemicals, of which mescaline is the most important. Dried cactus heads ("mescal buttons") have been used since pre-Columbian times in the religious ceremonies of native peoples in Mexico. About a century ago, this religious use spread to some tribes in the United States and Canada who, in 1922, became incorporated into the Native American Church. Other psychedelic drugs are synthetic. These include

  • lysergic acid diethylamide (LSD)
  • dimethoxymethylamphetamine (DOM or "STP")
  • methylenedioxymethamphetamine (MDMA or "ecstasy")

As their name suggests, DOM and MDMA also share the stimulant qualities of amphetamines. All the psychedelics have a molecular structure that resembles serotonin and probably bind to serotonin receptors on the postsynaptic membrane.

Phencyclidine (PCP)

PCP is used as an anesthetic in veterinary medicine. Used (illicitly) by humans (called "crystal" or "angel dust"), it can produce a wide variety of powerful reactions resembling those of stimulants as well as psychedelics. Unlike the other psychedelics, it binds to (and inhibits) NMDA receptors (in the hippocampus and other parts of the forebrain).

Marijuana

The main psychoactive ingredient in marijuana is delta-9-tetrahydrocannabinol9-THC). It binds to

  • CB1 receptors (G-protein-coupled receptors) that are present on presynaptic membranes in many parts of the brain.
  • CB2 receptors are also found in the brain as well as being highly-expressed on cells of the immune system (e.g., B cells and T cells).

THC produces the drowsiness of sedatives like alcohol, the dulling of pain (like opioids) and in high doses, the perception-distorting effects of the psychedelics. Unlike sedatives and opioids, however, tolerance to THC does not occur. In fact, the drug is excreted so slowly from the body that, with repeated use, a given response is achieved by a lower dose.

The natural ligands of the CB receptors are the endocannabinoids - anandamide and 2-arachidonylglycerol (2-AG). Both of these compounds are produced from phospholipids.

What are these natural ligands doing? They probably will turn out to have multiple effects, but the clearest ones so far are their effects on

  • appetite. Mice given anandamide eat more than normal while those whose genes for the CB1 receptor have been "knocked out" eat less than normal.These findings will be no surprise to the ill humans (e.g., with cancer or AIDS) who find that marijuana improves their appetite. Rimonabant (Acomplia®), a drug that blocks the ability of the body's natural CB1 ligands to bind the CB1 receptor was sold for a time in Europe as an appetite suppressant. (Because of its side effects, it was never approved for use in the U.S. and was removed from the European market in 2008.)
  • development of correct synaptic connections in the embryonic brain. Mice whose genes for the CB1 receptor have been knocked out develop defects in the wiring pattern of interneurons in their brain (which may account for the cognitive defects that have been reported in the children of women who used marijuana during pregnancy).
  • neuronal activity in the adult brain. Mice whose genes for the CB1 receptor have been knocked out are more susceptible to epileptic seizures. Marijuana has been used for centuries to control epileptic seizures in humans.
  • suppressing contact dermatitis. Knockout mice lacking CB1 and CB2 receptors mount a more vigorous allergic inflammatory response to agents (like nickel) that elicit contact sensitivity.

Systems-level view of cocaine addiction: the interconnection of the immune and nervous systems

The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction.

Keywords: Cocaine addiction immune system metabolism nervous system signaling.

© 2014 by the Society for Experimental Biology and Medicine.

Figures

Schematic representation of the signaling…

Schematic representation of the signaling of N,N-dimethyltryptamine (DMT) by vesicular release from the…

Summary of effects of cocaine…

Summary of effects of cocaine on immune function. Both up and down arrows…

A) Brain-immune bi-directional connections: the…

A) Brain-immune bi-directional connections: the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic…


Clinical Neurology, Clinical Research Neurologists, Clinical Psychologists, Psychiatry, Neuroscience

Chapter One. Drug Use and Its Consequences

2.1 Drugs and Consequences

Chapter Two. Genetics of Substance Use, Abuse, Cessation, and Addiction: Novel Data Implicate Copy Number Variants

2.1 Working Hypothesis I: Genomic Variants of Several Classes and Differing Frequencies Contribute to Vulnerability to Addiction and Ability to Quit

2.2 Working Hypothesis II: Genomic Variants that Contribute to Vulnerability to Addiction and Ability to Quit Provide Largely Additive Influences

2.3 Working Hypothesis III: Most Genomic Variants that Contribute to Dependence or Ability to Quit Exert Effects of Small Size, Though There are Larger Influences in Specific Populations and for Addiction-Associated Phenotypes

2.4 Working Hypothesis IV: There are Robust Overall Genetic Influences on Vulnerability to Dependence, Many Shared across Vulnerabilities to Different Substances. There are Robust Overall Genetic Influences on Ability to Quit, Some of Which Overlap with Those that Determine Degree of Dependence

Chapter Three. Epidemiology of Drug Abuse: Building Blocks for Etiologic Research

Chapter Four. Detection of Populations At-Risk or Addicted: Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Clinical Settings

2.3 Prevention and Intervention

Chapter Five. Cocaine: Mechanism and Effects in the Human Brain

2.2 Imaging Cocaine Abuse in the Human Brain

2.3 Imaging Cocaine: Behavioral Correlates

2.4 Dopamine Transmission in Striatal Subdivisions

Chapter Six. Stress, Anxiety, and Cocaine Abuse

2.1 Neurotransmitter Systems in Cocaine Withdrawal-Induced Anxiety and Stress-Induced Relapse

2.3 Corticotropin Releasing Factor

Chapter Seven. The Neuropathology of Drug Abuse

2.1 Neurobiological Basics of Drug Abuse

2.2 CNS Alterations of the Major Drugs of Abuse

2.3 Opioids and Derivatives

2.5 Amphetamines, Methamphetamine, and Designer Drugs

2.6 Amphetamine and Methamphetamine Derivatives

2.7 Neuropathological Investigations of (Poly-) Drug Abusers

2.8 Neurodegeneration and Drugs of Abuse

Chapter Eight. The Pathology of Methamphetamine Use in the Human Brain

2.1 Does Methamphetamine, a Dopamine Releaser, Cause Loss of Dopamine Neuronal Markers in Human Brain as Observed in Animal Studies?

2.2 Nondopaminergic Changes in Brain of Methamphetamine Users

2.3 Does Methamphetamine Cause Oxidative Stress in Human Brain?

2.4 Does Methamphetamine Cause Gliosis (Activated Microgliosis and Reactive Astrogliosis), a Reputed Index of Neurotoxicity, in Human Brain?

2.5 Does Methamphetamine Cause Holes in Human Brain or a Larger (Glial-filled) Brain?

2.6 Does Methamphetamine Cause Parkinson’s Disease or Persistent Psychosis Pathologies?: Epidemiological Findings

Recommendations for Future Studies

Chapter Nine. The Effects of Alcohol on the Human Nervous System

2.1 The Neurobiology of Alcohol

2.5 Wernicke–Korsakoff’s Syndrome

2.6 Neuroimaging and Alcohol-Induced Brain Changes

2.7 Alcohol-Related Neuropathy

Chapter Ten. The Nicotine Hypothesis

Chapter Eleven. Smoking Effects in the Human Nervous System

2.1 Nicotinic Acetylcholine Receptors

2.2 The Effects of Nicotine on naChRs in the Human Brain

2.3 Effect of nAChr Activation on Other Neurotransmitters in Human CNS

Chapter Twelve. Cognitive Effects of Nicotine

2.1 Cognitive Effects of Nicotine in Humans

2.2 Neurobiology of the Cognitive Effects of Nicotine

Chapter Thirteen. Effects of Cannabis and Cannabinoids in the Human Nervous System

2.1 Actions and Effects of Endocannabinoids and Cannabis

Chapter Fourteen. Cannabis, Cannabinoids, and the Association with Psychosis

2.1 Transient Behavioral and Cognitive Effects of Cannabinoids: Nonexperimental Evidence

2.2 Transient Behavioral and Cognitive Effects of Cannabinoids: Experimental Evidence

2.3 Effects of Cannabinoids on Schizophrenia Patients

2.4 Effects of Cannabinoids on Brain Structure and Function

2.5 Persistent Behavioral and Cognitive Effects of Cannabinoids

2.6 Cannabinoids, Psychosis, and Causality

2.7 The Effects of Cannabinoids on Neurodevelopment

Chapter Fifteen. Effects of MDMA on the Human Nervous System

2.4 Lasting Consequences of MDMA Exposure

Chapter Sixteen. Sedative Hypnotics

2.1 Historical Perspective

2.2 Mechanism of Action of Sedative Hypnotics

2.3 Clinical Use of Benzodiazepines

2.5 Introduction to the Z-Drugs: Nonbenzodiazepine GABA Receptor Agonists

Chapter Seventeen. Hallucinogens

2.1 Pharmacology, Antagonists, and Neuroanatomy of Hallucinogen Action

2.2 Neuroanatomy of Hallucinogens

2.3 Hallucinogens in Medicine

Chapter Eighteen. Inhalants: Addiction and Toxic Effects in the Human

2.1 How and Why Are They Used?

2.3 What Are the Medical Consequences of Abuse?

2.4 Pharmacological Properties/Effects

2.6 Recovery Potential and Treatment

Chapter Nineteen. Emerging Designer Drugs

2.1 Types of Designer Drugs

2.3 Synthetic Cannabinoids


COCAINE, DOPAMINE, AND THE LIMBIC SYSTEM

Cocaine produces dopamine buildup wherever the brain has dopamine transporters. However, its ability to produce pleasure and euphoria, loss of control, and compulsive responses to drug-related cues can all be traced to its impact on the set of interconnected regions in the front part of the brain that make up the limbic system (Hyman and Malenka, 2001 Kalivas and McFarland, 2003 Koob, Sanna, and Bloom, 1998 Nestler, 2001). Dopamine-responsive cells are highly concentrated in this system, which controls emotional responses and links them with memories.

One particular part of the limbic system, the nucleus accumbens (NAc), seems to be the most important site of the cocaine high. When stimulated by dopamine, cells in the NAc produce feelings of pleasure and satisfaction. The natural function of this response is to help keep us focused on activities that promote the basic biological goals of survival and reproduction. When a thirsty person drinks or someone has an orgasm, for example, dopaminergic cells flood the NAc with dopamine molecules. The receiving cells’ response makes us feel good and want to repeat the activity and reexperience that pleasure.

By artificially causing a buildup of dopamine in the NAc, as described above, cocaine yields enormously powerful feelings of pleasure. The amount of dopamine connecting to receptors in the NAc after a dose of cocaine can exceed the amounts associated with natural activities, producing pleasure greater than that which follows thirst-quenching or sex. In fact, some laboratory animals, if given a choice, will ignore food and keep taking cocaine until they starve.

The limbic system also includes important memory centers, located in regions called the hippocampus and amygdala. These memory centers help us remember what we did that led to the pleasures associated with dopamine release in the NAc𠅏or example, where we found water and how we attracted a mate. When someone experiences a cocaine high, these regions imprint memories of the intense pleasure as well as the people, places, and things associated with the drug. From then on, returning to a place where one has taken cocaine or merely seeing images of cocaine-related paraphernalia triggers emotionally loaded memories and desire to repeat the experience. Scientists believe that repeated cocaine exposure, with its associated dopamine jolts, alters these cells in ways that eventually convert conscious memory and desire into a near-compulsion to respond to cues by seeking and taking the drug.

A third limbic region, the frontal cortex, is where the brain integrates information and weighs different courses of action. The frontal cortex acts as a brake on the other regions of the limbic system when we decide to forgo a pleasure in order to avoid its negative consequences. Activity here can help a nonaddicted person heed the disastrous prognosis of continued cocaine abuse and suppress drug-taking urges emanating from the NAc, hippocampus, and amygdala. Once someone becomes addicted, however, the frontal cortex becomes impaired and less likely to prevail over the urges (Nestler and Malenka, 2004 Volkow, Fowler, and Wang, 2003).


Drugs and Their Effects

For the exam you need to be familiar with the following types of drugs and the effects they can have on the body.

Stimulants

A stimulant is a drug that increases the activity of the nervous system. It can raise the alertness, emotions or mood.

Caffeine is a mild stimulant found in tea and coffee. It is pretty harmless and most peoples' lives are not affected by it. Prolonged overuse may lead to problems with the heart, stomach and pancreas.

Amphetamine and methedrine are stronger stimulants. They induce a feeling of boundless energy but there is a deep depression after their use.

People think that they are performing better than they actually are.

The person rapidly becomes dependent and needs the drugs to maintain the highs. Continued usage can lead to personality changes and serious depression.

Depressants

Depressants reduce the activity of the nervous system. They slow down your responses and make you sleepy.

Alcohol and barbiturates can cause slowed reaction times and poor judgement of speed and distance. They can lead to increased risk of accidents.

Barbiturates are used as tranquillisers. Overdosing can stop you breathing. Not a good idea.

Hallucinogens

A hallucination is a weird interpretation of the world around you. LSD and Ecstasy can cause these, usually only with higher doses of Ecstasy.

At lower doses Ecstasy gives a feeling of boundless energy and universal love, but this mood - changing effect can lead to a growing dependence.

The feeling of energy leads to a danger of overheating, dehydration and collapse.

Solvents

These include a variety of chemicals found in everyday things like paint, glue and gas canisters. They affect your nervous system and heart.

Solvents can cause hallucinations and can have very serious effects on body and personality. They cause damage to the kidneys, lungs, brain and liver.

There is also a high risk of sudden death.

Pain killers

These are useful medical drugs used by doctors to control patients' pain.They stop the impulses from pain receptors and neurones reaching the brain.

However they are often misused and lead to strong dependence and physical deterioration. Also their cost on the street leads many into committing crime to be able to afford to buy them.

Heroin and morphine are powerful painkillers. They provide a feeling of sleepiness and calm when first taken. Over time the person loses all motivation. They fail to look after themselves and rapidly deteriorate physically and mentally.

Falling into crime is a major problem, including prostitution and theft.

Aspirin is also a painkiller, a very mild one. However, people do overdose on it, usually accidentally. It has harmful effects, including stomach bleeding. Yeugh!

Alcohol

In many cultures alcohol has awelcome and socially acceptable place. In limited use it helps to relax us. However if misused it has serious problems.

Contrary to popular belief, alcohol is a depressant. Initially it depresses your inhibitions, but then it depresses your consciousness and finally your essential functions. In other words, it can kill you!

The depressant effect leads to a loss of judgement that can lead to accidents and taking life-threatening risks.

It has a poisonous effect on the brain, liver and other organs. Long-term abuse can lead to cancer, memory loss and so on. It doesn't help your sex life either!

Alcohol dependence can see a downward spiral into loss of income, job, friends, family and life.

Alcohol abuse can wreck your life.

Tobacco

Once it was seen as the sophisticated and cool thing to use. Some still see smoking as cool and grown up.

However is now known to have very serious health risks. It kills 20,000 people a year in the UK alone. And you pay for the privilege!

If you spend £20 a week on tobacco it is costing you £1,040 a year. If you then smoke from the age of 16 until 65, you would have spent £51,000 on the habit. That's forgetting about inflation!

What about the health effects? The nicotine in tobacco affects the nervous system and is strongly addictive but does not really effect your mood. There's no 'high'.

There are also hundreds of cancer-causing chemicals in burning tobacco. These have been proved to cause lung cancers, heart and circulation problems.

The tar from tobacco clogs up your lungs and stops them working properly. This causes diseases like emphysema and bronchitis where the person has trouble getting enough breath.

The tar also stops the cilia that clear the lungs of mucus and bacteria from working. So you develop a lovely 'smokers cough' with all that yucky stuffin it. Hmmm. nice.

Some say that smoking helps keep them slim - but who wants to be slim, broke and smelly?

Now test yourself!

Click on the left and right arrow buttons until you think you have selected the correct answer, then click on "Mark answer" button:


How Heroin Affects the Nervous System and Brain

After your nervous system is consistently exposed to opioids and the subsequent elevated levels of dopamine, you adjust and develop a tolerance to heroin. This adjustment means that your threshold for pain is lowered, and your sensitivity to pain is higher. Some of these side effects may even begin as soon as after the first time you use the drug.

After you begin using heroin, your pathways that signal pain become overactive, and in this way, heroin affects the nervous system by creating the feeling that you need to keep using heroin to maintain a sense of normalcy.

Another way that heroin affects the nervous system is the fact that it depresses activity. This occurrence means it slows down vital functions of the brain and the entire nervous system, including respiration. This is what causes people to overdose from heroin.

How heroin affects the nervous system as a depressant also includes the fact that it can cause an irregular heart rate, and it can lower their body’s temperature and blood pressure.


This system connects the brain stem and spinal cord with internal organs and regulates internal body processes that require no conscious effort and that people are thus usually unaware of (see Overview of the Autonomic Nervous System). Examples are the rate and strength of heart contractions, blood pressure, the rate of breathing, and the speed at which food passes through the digestive tract.

The autonomic nervous system has two divisions:

Sympathetic division: Its main function is to prepare the body for stressful or emergency situations—for fight or flight.

Parasympathetic division: Its main function is to maintain normal body functions during ordinary situations.

These divisions work together, usually with one activating and the other inhibiting the actions of internal organs. For example, the sympathetic division increases pulse, blood pressure, and breathing rates, and the parasympathetic system decreases each of them.

Typical Structure of a Nerve Cell

A nerve cell (neuron) consists of a large cell body and nerve fibers—one elongated extension (axon) for sending impulses and usually many branches (dendrites) for receiving impulses.

Each large axon is surrounded by oligodendrocytes in the brain and spinal cord and by Schwann cells in the peripheral nervous system. The membranes of these cells consist of a fat (lipoprotein) called myelin. The membranes are wrapped tightly around the axon, forming a multilayered sheath. This myelin sheath resembles insulation, such as that around an electrical wire. Nerve impulses travel much faster in nerves with a myelin sheath than in those without one.

If the myelin sheath of a nerve is damaged, nerve transmission slows or stops. The myelin sheath may be damaged by various conditions that damage the brain or peripheral nerves including

Certain autoimmune disorders (such as Guillain-Barré syndrome)

Certain hereditary disorders


Drugs are chemicals that can alter the way the body works. There are different types of drugs, and they have different effects on the body.

Classification of Drugs

Some drugs are legal, such as tobacco and alcohol. Others are illegal, or must only be prescribed by a doctor. Some prescription drugs are misused and taken for recreational use, rather than for medical reasons. They become illegal under these circumstances.

Illegal drugs are classified from Class A to Class C. Class A drugs are the most dangerous, with the most serious penalties for possession or dealing. Class C are the least dangerous, with the lightest penalties, but this does not mean they are safe to use.

Stimulants and depressants

Stimulants and depressants affect the synapses between neurones in the nervous system:

  • stimulants cause more neurotransmitter molecules to diffuse across the synapse
  • depressants stop the next neurone sending nerve impulses – they bind to the receptor molecules it needs to respond to the neurotransmitter molecules.

Tobacco and Smoking

Cigarettes are harmful in three ways, they contain:

  • 1.Nicotine – addictive drug that leads to heart disease. Nicotine raises blood pressure and narrows arteries
  • 2. Tar – coats the lining of the lungs > less O2 is absorbed. Tar contains carcinogens which cause cancers
  • 3. Carbon monoxide – poisonous gas which joins onto red blood cells making them incapable of transporting oxygen around the body

Parkinson’s disease and smoking – is it worth the risk?

Parkinson’s disease is a disorder of the central nervous system that is caused by a loss of cells in an area of the brain. Those cells produce dopamine, a chemical messenger responsible for transmitting signals across synapses. Loss of dopamine causes some nerve cells to fire out of control, leaving patients unable to control their movement in a normal way.

Patients often start off with slight shaking of the hands and they may eventually have difficulty walking, talking or completing other simple tasks. The disease can be treated by giving a drug called L-dopa. The brain uses this chemical to make more dopamine. Unfortunately, the drug has a number of side effects and larger doses of the drug are often needed as the disease gets worse.

Patients therefore have a difficult decision to make. In recent studies on Parkinson’s disease it has been suggested that there is a correlation between smoking and a reduced risk of having the disease. Doctors are trying to find out if this means that smoking actually causes the protection.

Do these results mean that doctors are actually advising patients to smoke? No, they are not. As a doctor said:
“The dangers of cigarette smoking far outweigh any as yet inconclusive evidence that there are advantages of protection from Parkinson's disease. You need to look at the risks – smoking is the largest single cause of preventable death in many countries. About 1 in 1000 people are likely to get Parkinson’s disease but every year over 100 000 people die through cigarette smoking in the UK. Smoking is just not worth the risk.”

The alcohol in alcoholic drinks - such as wines, beers and spirits - is called ethanol. It is a depressant. This means that it slows down signals in the nerves and brain.

There are legal limits to the level of alcohol that drivers and pilots can have in the body. This is because alcohol impairs the ability of people to control their vehicles properly. Breath tests and blood tests are used by the police to see if a driver is over the limit.

The liver removes alcohol from the bloodstream. It has enzymes that break down alcohol but the products of the reactions involved are toxic. They damage the liver and over time this leads to cirrhosis.


Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality

Gene transfer has long been a compelling yet elusive therapeutic modality. First mainly considered for rare inherited disorders, gene therapy may open treatment opportunities for more challenging and complex diseases such as Alzheimer's or Parkinson's disease. Today, examples of striking clinical proof of concept, the first gene therapy drugs coming onto the market, and the emergence of powerful new molecular tools have broadened the number of avenues to target neurological disorders but have also highlighted safety concerns and technology gaps. The vector of choice for many nervous system targets currently is the adeno-associated viral (AAV) vector due to its desirable safety profile and strong neuronal tropism. In aggregate, the clinical success, the preclinical potential, and the technological innovation have made therapeutic AAV drug development a reality, particularly for nervous system disorders. Here, we discuss the rationale, opportunities, limitations, and progress in clinical AAV gene therapy.

Keywords: AAV adeno-associated virus astrocyte gene therapy gene transfer immunity nervous system neuron vector.


SUMMARY

Opioid dependence and addiction are most appropriately understood as chronic medical disorders, like hypertension, schizophrenia, and diabetes. As with those other diseases, a cure for drug addiction is unlikely, and frequent recurrences can be expected but long-term treatment can limit the disease’s adverse effects and improve the patient’s day-to-day functioning.

The mesolimbic reward system appears to be central to the development of the direct clinical consequences of chronic opioid abuse, including tolerance, dependence, and addiction. Other brain areas and neurochemicals, including cortisol, also are relevant to dependence and relapse. Pharmacological interventions for opioid addiction are highly effective however, given the complex biological, psychological, and social aspects of the disease, they must be accompanied by appropriate psychosocial treatments. Clinician awareness of the neurobiological basis of opioid dependence, and information-sharing with patients, can provide insight into patient behaviors and problems and clarify the rationale for treatment methods and goals.



Comments:

  1. Mbizi

    An interesting topic, I will take part. I know that together we can come to the right answer.

  2. Kigashicage

    . Rarely. You can say this exception :)

  3. Kalyan

    What a useful topic

  4. Mezill

    Where do you get the info for posts if it's not a secret?

  5. Macniall

    Bravo, you just visited another idea



Write a message