Chronic morphine induces long-lasting changes in acetylcholine release in rat nucleus accumbens core and shell: an in vivo microdialysis study

Previously, only in vitro studies have shown that chronic administration of morphine provokes longlasting enhanced activity of accumbal cholinergic ne urons, which may contribute to the behavioural sensitization, positive rein forcement and aversive effects associated with enhanced drug-seeking. The p resent study was aimed at clarifying whether these adaptive changes would a lso be supported by in vivo microdialysis measurements in freely moving rat s, distinguishing between the accumbal substructures shell and core, and ob serving behavioural changes simultaneously. Acute administration of morphin e dose-dependently decreased acetylcholine (ACh) release in the nucleus acc umbens (NAc), with 10 mg/kg SC being most effective, 5 mg/kg ineffective. O n day 5 of spontaneous abstinence from chronic morphine treatment (10-40 mg /kg morphine dose once daily for 5 days), when withdrawal symptoms were sti ll present, even a lower morphine dose (5 mg/kg) was effective in decreasin g ACh release in the NAc. During the later phase of abstinence, when no wit hdrawal symptoms were detectable, the opposite effect, i.e. an increase of ACh release was found. This later effect may represent a longlasting neuroa daptive effect of morphine. These adaptive effects seemed to be more promin ent in the NAc shell. Concurrent with these changes in ACh release, morphin e challenges produced marked behavioural stereotypes, possibly indicating b ehavioural sensitization.