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KEY CONCEPTS

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  • The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences.

  • Addictive drugs induce pleasurable states or relief from distress, thus motivating repeated drug use.

  • Drugs of abuse are both rewarding and reinforcing. Rewards are stimuli that the brain interprets as intrinsically positive, and reinforcing stimuli are those that increase the probability that behaviors paired with them will be repeated.

  • The brain reward circuitry targeted by addictive drugs, which normally responds to natural reinforcers such as food and sex, includes the dopaminergic projections from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens (NAc) and other forebrain structures.

  • Repeated use of addictive drugs produces multiple unwanted changes in the brain that may lead to tolerance, sensitization, dependence, and addiction.

  • Dependence is an adaptive state that develops in response to repeated drug administration; when unmasked by cessation of drug use, this adapted state may lead to withdrawal symptoms.

  • Tolerance refers to the diminished effect of a drug after repeated administration at the same dose, or to the need for an increase in dose to produce the same effect; sensitization describes the opposite response to repeated drug administration.

  • Cocaine and amphetamines produce their psychoactive effects by potentiating monoaminergic transmission through actions on the dopamine transporter, together with actions on the serotonin and norepinephrine transporters.

  • The reinforcing effects of opiate drugs result from their binding to endogenous opioid receptors, most importantly μ opioid receptors in both the VTA and NAc.

  • The immediate effects of ethanol are believed to result primarily from facilitation of GABAA receptors and inhibition of NMDA glutamate receptors. At higher doses, ethanol inhibits the functioning of many ion channels as well.

  • The effects of nicotine are caused by its activation of nicotinic acetylcholine (nACh) receptors; its reinforcing effects depend in part on nACh receptors located on VTA dopamine neurons.

  • Delta-9-tetrahydrocannabinol, the active psychotropic ingredient in marijuana, exerts its primary pharmacologic effects by binding to a G protein–coupled receptor in the brain known as the CB1 receptor.

  • The psychotomimetic drugs of abuse, phencyclidine (angel dust, PCP) and ketamine, bind specific sites in the channel of the NMDA glutamate receptor, where they act as noncompetitive NMDA antagonists.

  • Drugs of abuse cause addiction by inducing a range of molecular and cellular adaptations in several brain reward regions, which are becoming increasingly well known.

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INTRODUCTION

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Drug addiction is a progressive and often fatal behavioral syndrome characterized by compulsive drug seeking and consumption despite serious negative consequences. The drug-centered existence of addicts can cost them their jobs, personal relationships, financial standing, happiness, and, in some cases, their lives. Drug-addicted individuals often appear to have lost the ability to make choices that promote their own happiness and survival. Many drug addicts who seek treatment report that they realize the destructive nature of their addiction but are unable to alter their addictive behavior.

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In laboratory settings in which social and environmental ...

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