Drug-induced place preference in rats with 5,7-dihydroxytryptamine lesions of the nucleus accumbens.

The conditioned place preference (CPP) paradigm was used to determine a role for serotonin in the nucleus accumbens in the mediation of the rewarding properties of D-amphetamine morphine and diazepam. The effect of these drugs on CPP was examined in controls and in animals with 5,7-dihydroxytryptamine lesions of the nucleus accumbans. The results from control animals confirmed that D-amphetamine (1.5 mg/kg, i.p.), morphine (2.0 mg/kg, i.p.) and diazepam (1.0 mg/kg, i.p.) produced place preference for a distinctive environment that had previously been paired with injections of the drug. In animals with 80% reduction of 5-hydroxytryptamine content of the nucleus accumbens, D-amphetamine CPP was unchanged and morphine CPP was attenuated compared with controls. Diazepam CPP was not apparent in animals with the lesion. In separate experiments, characteristic behavioural effects of the drugs under study were examined in control and in animals with lesion. The results showed a tendency for increased amphetamine hyperlocomotion, enhanced morphine activity and analgesia and decreased diazepam anti-anxiety effect in animals with lesions. Thus, the 5,7-dihydroxytryptamine lesions of the nucleus accumbens differently influenced the CPP induced by the drugs studied and, with the exception of diazepam, the various behavioural effects elicited by each drug. The findings suggest that serotonin-containing neurones of the nucleus accumbens are a component of the neural circuitry that mediates the rewarding properties of morphine, probably of diazepam, but not of D-amphetamine.