Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome.
The nucleus accumbens is prominently implicated in the reinforcing effects of abused drugs, and is an important site for mediating aversive stimulus properties of opiate withdrawal. It is generally thought, however, that the role of the accumbens is negligible in the somatic signs of opiate withdrawal. Contrary to this assumption, we now report that D2 dopaminergic receptor activity in the accumbens area potently regulates somatic symptoms of opiate withdrawal. We find that activation of D2 receptors within the accumbens prevents somatic signs of naloxone-induced opiate withdrawal and, conversely, that blockade of accumbal D2 receptors in opiate-dependent animals elicits somatic withdrawal symptoms. These data indicate that dopamine in the accumbens not only is important in the rewarding effects of abused drugs, but also (via D2 receptors) plays a pivotal role in opiate withdrawal.
Harris
G C
GC
Department of Mental Health Sciences, Hahnemann University, Philadelphia, Pennsylvania 19102.
Aston-Jones
G
G
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D008297:Male; D009270:Naloxone; D009294:Narcotics / Q000009:adverse effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D009294:Narcotics; D017448:Receptors, Dopamine D2; D009270:Naloxone; D004298:Dopamine