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The Human Nucleus Accumbens Is Highly Susceptible to G Protein Down‐Regulation by Methamphetamine and Heroin
Author(s) -
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.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0742120.x
Subject(s) - nucleus accumbens , methamphetamine , heroin , addiction , neuroscience , brain stimulation reward , pharmacology , drug , medicine , dopamine , psychology , biology
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 Gα i1 and/or Gα i2 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 Gα i ‐linked receptor activity.