Effects of serotonergic activity in nucleus accumbens septi on drug-induced circling.

The effects of injections of 5-hydroxytryptamine (5-HT) into the nucleus accumbens and lesions of the nucleus accumbens induced by 5,7-dihydroxytryptamine (5,7-DHT) on drug-induced circling were investigated in rats with unilateral nigrostriatal lesions induced by 6-hydroxydopamine (6-OHDA). Injections of 5-HT (60-120 micrograms in 1 microliter; 1 microliter/min) into the nucleus accumbens caused a significant decrease in the circling response to 5.0 mg/kg of d-amphetamine (s.c.). The distribution of radioactivity after intracerebral injections of [3H]5-HT using these parameters showed that although much of the injected material was retained in the nucleus accumbens there was also considerable spread to the frontal cortex. However, in further behavioural experiments, using an injection procedure (0.5 microliter; 0.11 microliter/min) which caused much greater retention of injected material in the nucleus accumbens, with minimal spread to the frontal cortex, the ability of 5-HT injected into the accumbens to block amphetamine-induced circling was not diminished. Moreover, injections of 5-HT into the frontal cortex did not have any effect on amphetamine-induced circling. Lesions of the nucleus accumbens induced by 5,7-DHT caused a significant enhancement of the contralateral circling response to 1.0 mg/kg of apomorphine and a similar but non-significant tendency to increase the circling responses to several other doses of apomorphine and amphetamine. The results provide evidence that serotonergic mechanisms in the nucleus accumbens inhibit circling behaviour generated by unilateral activation of nigrostriatal dopaminergic mechanisms.