When injected into the fimbria-fornix/cingular bundle, not in the raphe, 5,7-dihydroxytryptamine prevents amphetamine-induced hyperlocomotion

The locomotor effects of acute amphetamine treatment (1 mg/kg, i.p.) were a ssessed in Long-Evans rats after 5,7-dihydroxytryptamine (5,7-DHT) injectio ns into the fimbria-fornix/cingular bundle (FiFx/CB; 4 mu g/side), or the d orsal and median raphe (Raphe; 10 mu g). In control rats, amphetamine induc ed a significant increase of home-cage activity for about 2 h. This effect was similar in Raphe rats, but was absent in FiFx/CB rats. The raphe lesion s reduced serotonin concentrations by 50% in the dorsal hippocampus, 75% in the ventral hippocampus and 58% in the fronto-parietal cortex. After FiFx/ CB lesions, the reduction amounted 50, 61 and only 25%, in each of these re gions, respectively. In the fronto-partietal cortex, dopamine concentration was significantly decreased in Raphe (- 27%) and FiFx/CB rats (- 65%). The results suggest that a serotonergic denervation of the hippocampus by inje ctions of 5,7-DHT into the FiFx/CB pathways hampers the stimulating effects of amphetamine on locomotor activity. This effect might be related to the reduced dopaminergic tone in the fronto-parietal cortex. (C) 2000 Elsevier Science B.V. All rights reserved.