Drugs of abuse and the brain
by
Leshner AI, Koob GF
National Institute on Drug Abuse,
National Institutes of Health,
Rockville, MD, USA.
Proc Assoc Am Physicians 1999 Mar-Apr; 111(2):99-108

ABSTRACT

New insights into our understanding of drug abuse and addiction have revealed that the desire to use drugs and the process of addiction depend on effects on brain function. Drugs of abuse have been hypothesized to produce their rewarding effects by neuropharmacological actions on a common brain reward circuit called the extended amygdala. The extended amygdala involves the mesolimbic dopamine system and specific subregions of the basal forebrain, such as the shell of the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala. The psychomotor stimulants cocaine and amphetamine activate the mesolimbic dopamine system; opiates activate opioid peptide receptors within and independent of the mesolimbic dopamine system. Sedative hypnotics alter multiple neurotransmitter systems in this circuitry, including: 1) gamma aminobutyric acid; 2) dopamine; 3) serotonin; 4) glutamate; and 5) opioid peptides. Nicotine and tetrahydrocannabinol both activate mesolimbic dopamine function and possibly opioid peptide systems in this circuitry. Repeated and prolonged drug abuse leads to compulsive use, and the mechanism for this transition involves, at the behavioral level, a progressive dysregulation of brain reward circuitry and a recruitment of brain stress systems such as corticotropin-releasing factor. The molecular mechanisms of signal transduction in these systems are a likely target for residual changes in that they convey allostatic changes in reward set point, which lead to vulnerability to relapse.

CRF
GABA
Genes
Reward
Alcohol
Cocaine
Tobacco
Cannabis
Anhedonia
GBR12909
Drug addiction
NMDA antagonists
Dopamine and sex
Mesolimbic dopamine
The nucleus accumbens
Bipolar versus unipolar
CRF and drug addiction
The neural basis of addiction
Novelty reward and anhedonia
Dopamine and reward signalling
The reward system in depression
Depression, dopamine and dextroamphetamine
Mesolimbic medium spiny neurons and pleasure
Regulation of synapses in the nucleus accumbens
The nucleus accumbens: opioids versus cannabinoids
Dopamine's role in reward: the case for incentive salience

Refs
and further reading

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