The Human Nucleus Accumbens Is Highly Susceptible to G Protein Down‐Regulation by Methamphetamine and Heroin

• Published in: Journal of neurochemistry 2000-05, Vol.74 (5), p.2120-2126
• Main Authors: McLeman, Elizabeth R., Warsh, Jerry J., Ang, Lee, Li, Peter P., Kalasinsky, Kathleen S., Ross, Brian M., Tong, Junchao, Schmunk, Gregory, Adams, Vernard, Kish, Stephen J.
• Format: Article
• Language: English
• Subjects: Adult; Brain - metabolism; Cadaver; Central Nervous System Stimulants - pharmacology; Cocaine; Cocaine - pharmacology; Dopamine; Down-Regulation; Female; G protein; GTP-Binding Proteins - antagonists & inhibitors; GTP-Binding Proteins - metabolism; Heroin; Heroin - pharmacology; Humans; Male; Methamphetamine; Methamphetamine - pharmacology; Narcotics - pharmacology; Nucleus accumbens; Nucleus Accumbens - metabolism; Reference Values; Substance-Related Disorders - metabolism
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2000.0742120.x

: Although the nucleus accumbens is assumed to be a critical brain “pleasure center,” its function in humans is unknown. As animal data suggest that a unique feature of this small brain area is its high sensitivity to down‐regulation of an inhibitory G protein by drugs of abuse, we compared G protein levels in postmortem nucleus accumbens with those in seven other brain regions of chronic users of cocaine, methamphetamine, and heroin, and of matched controls. Biochemical changes were restricted to the nucleus accumbens in which concentrations of Gαi1 and/or Gαi2 were reduced by 32‐49% in the methamphetamine and heroin users. This selective responsiveness to these abused drugs implies a special role for the human nucleus accumbens in mechanisms of drug reinforcement and suggests that some features of the drug‐dependent state (e.g., tolerance) might be related to inhibition of Gαi‐linked receptor activity.