Dispelling the Myths About Addiction Strategies to Increase Understanding and Strengthen Research (1997) / Chapter Skim
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3 Neurobiology of Addiction: An Overview
3 Neurobiology of Addiction: An Overview
Pages 37-54
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From page 37... ...
The role of dopamine as a neurotransmitter in the brain reward circuitry is highlighted in this chapter, because it relates to the four classes of drugs discussed in this report nicotine, alcohol, stimulants, and opioids. Although there are some important differences among them, these drugs share common reward pathways in the brain.
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From page 38... ...
Selfadministration models are particularly useful in studying the behavioral patterns and consequences of ethanol ingestion. The finding that food deprivation leads to increased ethanol intake in ethanol self-administration models provides a better understanding of the relationship between drug use and eating disorders.
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From page 39... ...
THE BRAIN'S COMMON "REWARD" PATHWAY Two lines of investigation led to the conclusion that addictive drugs, although chemically different from one another, all affect a brain system involved in the control of motivated behavior. The first set of experiments were performed in rats in the 1950s and involved stimulating discrete brain regions (Olds and Milner, 1954~.
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From page 40... ...
The second set of clues concerning the substrates of addiction came from more recent work which showed that each of these highly addictive drugs mimics or enhances the actions of one or more neurotransmitters in the brain that are involved in the control of the brain reward circuit (Cooper et al., 1996~. The opioids mimic endogenous opioid-like compounds called endorphins; cocaine and related drugs enhance the actions of dopamine itself; nicotine mimics the action of acetylcholine (another transmitter)
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From page 41... ...
The firing rate of VTA dopamine neurons is held at a certain "tonic" or stable level by inhibitory neurons. These inhibitory neurons, in turn, possess opioid receptors.
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From page 42... ...
NOTE: NAc = nucleus accumbens; VTA = ventral segmental area. EMOTION, MEMORY, AND THE TRANSITION FROM USE TO ADDICTION In addition to the reward pathways, the human brain contains multiple circuits that are involved in the processing of emotion, learning, and conditioning.
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From page 43... ...
Chronically, ethanol causes long-term neuroadaptive changes in the function of the GABAAbenzodiazepine receptor complex and the NMDA-glutamate receptor complex, which contribute to the production of chronic tolerance. A second group of signal transduction pathways that ethanol affects are the G-protein coupled and adenylate cyclase related receptors, whose activating ligands include the opioid peptides, dopamine, serotonin, and adenosine.
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From page 44... ...
Thus, the dopaminergic reward pathway likely plays a role in assigning novel stimuli to specific adaptive behavioral repertoires. By perverse serendipity, this adaptive emotional circuit makes brains vulnerable to drug addiction because certain addictive drugs mimic or enhance the actions of neurotransmitters used within it.
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From page 45... ...
The denial, manipulation, and dishonesty that the addicted person frequently exhibits in the service of ongoing drug use may frustrate and anger family members, colleagues, and caregivers. A key point in our current understanding of the neurobiology of drug abuse is that there is good evidence that use of a drug at an adequate dose with adequate frequency and chronicity produces long-lived changes in brain functioning.
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From page 46... ...
A third category of long-term alteration in brain function that may be produced by addictive drugs in some individuals is the production of powerful "emotional memories" of drug use. There is increasing evidence to suggest that things reamed in the context of strong emotional activation are most indelibly etched into distinct memories.
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From page 47... ...
The flush reaction may represent a physiological "protective" factor that tends to prevent affected individuals from developing an alcohol addiction. The biological basis of this flush reaction is a variation in two genes that code for two principal enzymes of alcohol metabolism, alcohol dehydrogenase (ADH)
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From page 48... ...
The study of environmental factors that produce risk versus resilience with respect to drug addiction' however, must contend with multiple behavioral, psychological, and social factors that complicate analysis. In addition, other factors influence drug taking, including drug availability, acceptability in the individual's subculture, behavioral alternatives to drug use, and presence of other psychiatric illness.
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From page 49... ...
The idea that addictive drugs may commandeer key motivational circuits in the brain should also help researchers, physicians, and others to understand some of the otherwise inexplicable behavior of addicted people, who continue to use drugs either openly or surreptitiously despite, in many cases, tremendously negative personal and social consequences. This model also implies the importance of prevention and underlines the fact that, for those who are most severely affected, recovery may never be complete when environmental cues can always engender intense cravings and risk of relapse.
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From page 50... ...
ance Determination of the neurobiological basis of nicotine reinforcement Molecular studies identifying genes, posttranslational modifications, or signal transduction pathways that produce functional subtypes of mu, kappa, and delta opioid receptors . Development of selective agonists or antagonists of kappa and delta opioid receptors for use in humans · Further characterization and evaluation of vaccine approaches to cocaine addiction · Identification of genes and quantitative tract loci associated with alcoholrelated phenotypes in animal models Elucidation of neurobiology and molecular biology underlying alcohol toler Use of transgenic and gene knockout animal models to evaluate alcohol responses on brain neurotransmitter and reward systems .
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From page 51... ...
1994. Genetic animal models of alcohol and drug abuse.
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From page 52... ...
1996. Drug addiction: The yin and yang of hedonistic homeostasis.
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From page 53... ...
1996. Drug addiction and drug abuse.
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