The D3 dopamine receptor and substance dependence

Behavioral sensitization, the progressive and enduring enhancement of certa in stimulant-induced behaviors following repetitive drug use, is mediated i n part by dopaminergic pathways known to play a role in drug dependence. It has been theorized that sensitization underlies the development of drug cr aving and initiates addictive behaviors of drug dependence, We propose that down-regulation of D3 dopamine receptor function contributes to sensitizat ion. Rodent locomotion is regulated by the opposing influence of dopamine r eceptor subtypes, with D3 stimulation inhibiting and concurrent D1/D2 recep tor activation stimulating locomotion. The D3 receptor has greater occupanc y than D1 or D2 receptors following stimulant drug administration. Sensitiz ation may therefore result in part from greater accommodation of the inhibi tory D3 receptor "brake" on locomotion, leading to progressive locomotion i ncrease following repeated stimulant exposure. Further study is needed to t est this proposed model, and to clarify the role of individual dopamine rec eptor subtypes in sensitization and drug dependence. (C) 2001 by The Hawort h Press, Inc.