REDUCED DOPAMINE OUTPUT IN THE NUCLEUS-ACCUMBENS BUT NOT IN THE MEDIAL PREFRONTAL CORTEX IN RATS DISPLAYING A MECAMYLAMINE-PRECIPITATED NICOTINE WITHDRAWAL SYNDROME

Mesolimbocortical dopamine (DA) neurotransmission is important in the mediation of the dependence-producing actions of nicotine and other dr ugs of abuse. Withdrawal from chronic treatment with various types of addictive drugs, including amphetamine, cocaine, ethanol and morphine is associated with a decrease in dopaminergic output in the nucleus ac cumbens (NAG), whereas the effects of withdrawal from these drugs on d opaminergic output in the medial prefrontal cortex (PFC), as yet, rema in largely unknown. This study examined putative changes in the extrac ellular levels of dopamine and its metabolites dihydroxyphenylacetic a cid (DOPAC) and homovanillic acid (HVA) in the NAC and in the PFC of r ats displaying behavioral signs of nicotine withdrawal. Rats were infu sed for 7 days with nicotine via subcutaneously implanted minipumps, w hereas control animals carried saline-containing pumps. On the fifth d ay of infusion a microdialysis probe was implanted in the NAC or the P FC of the rats. Forty-eight hours later the levels of DA and the monoa mine metabolites were assessed in the dialysate. The behavioral and bi ochemical effects of a saline injection and a subsequent challenge wit h the nicotinic receptor antagonist mecamylamine (1 mg/kg s.c.) were d etermined. Following mecamylamine challenge in nicotine-treated animal s, the levels of DA, DOPAC and HVA in the NAG, but not in the PFC, dec reased below pre-injection levels and in relation to control animals. The score of abstinence signs increased in the nicotine-treated rats, as compared both to the score after saline and to that in control anim als. The decreased DA output in the NAC in animals displaying nicotine withdrawal signs is similar to that seen after withdrawal of several other drugs of abuse, and may have bearing on motivational deficits as sociated with the abstinence reactions. (C) 1998 Elsevier Science B.V.