Effect of p-chloroamphetamine and 5,7-dihydroxytryptamine on rotation and dopamine turnover.

Injections of p-chloroamphetamine (PCA) or 5,7-dihydroxytryptamine (DHT) (after pretreatment with desmethylimipramine) into the median raphe nucleus (MRN) caused depletions of 5-HT and 5-HIAA in the cortex and striatum, and a decrease of cortical 5-HT uptake without affecting NE uptake. Unilateral injections of these neurotoxins into the MRN caused contralateral rotation, which was blocked by haloperidol. The size of the lesion correlated with the rate of rotation and the decrease in 5-HT turnover in the cortex. We also found a significant correlation between the rate of rotation and the decrease in cortical 5-HT turnover, and the increase in striatal DA turnover. Moreover, there was a significant correlation between the decrease in cortical 5-HT turnover and the increase in striatal DA turnover. It was found that injections of DHT into the SN produced similar behavioral and biochemical changes as did the MRN lesions. In this model, amphetamine and apomorphine produce turning in the same direction, whereas they have opposite effects after lesions of the nigrostriatal pathway where postsynaptic DA supersensitivity occurs. Presynaptic changes appear to determine turning in this model. An inhibitory role of the serotonergic MRN on the dopaminergic nigrostriatal pathway mediated via the substantia nigra (SN) is suggested.