Unilateral destruction of dopamine pathways increases ipsilateral striatal serotonin turnover in rats

In order to evaluate the influence of dopaminergic transmission on regional brain utilization of serotonin (5HT), the effects of the destruction of the ascending dopamine (DA) pathways on regional brain 5HT metabolism in the rat were examined. Complete unilateral lesions of the nigrostriatal DA pathways (> 90% DA loss) were made by infusing the neurotoxin 6-hydroxy-dopamine into either the left medial forebrain bundle (MFB) or the left substantia nigra (SN). At 6 weeks after the lesions, levels of 5HT and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA), were determined bilaterally in the striatum, frontal cortex, and hypothalamus. In the striatum of the lesioned hemisphere, the 5HT level decreased by more than 50%, while the ratio of 5HIAA:5HT (an index of 5HT turnover) increased by more than 90%. In the same rats, cortical and hypothalamic 5HT, 5HIAA, and 5HT turnover were not changed as a result of the MFB or SN lesions. These results suggest that the loss of DA innervation in the striatum triggers an increase in 5HT turnover and a net depletion of 5HT in the striatum. To verify that the loss of DA was responsible for the observed striatal 5HT changes, we examined the effect of intracerebral implantation of DA-containing pellets into one group of MFB-lesioned rats. The lesioned rats with placebo pellets did not differ from lesioned rats without pellets, whereas the implantation of DA pellets reversed the lesion-induced changes in the 5HT levels and 5HIAA:5HT ratios.(ABSTRACT TRUNCATED AT 250 WORDS)