Biochemical Evidence for Alteration of Neostriatal Dopaminergic Function by 5,7‐Dihydroxytryptamine

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Abstract
Unilateral injection of 5,7‐dihydroxytryptamine (DHT) into the rat neostriatum markedly reduced not only striatal tryptophan hydroxylase (TPH) activity but also striatal tyrosine hydroxylase (TH) activity and dopamine (DA) concentration measured 10‐15 days later. The decrease in striatal TH activity was dose related over the range of 8‐32 pg of DHT; a dose of 16 pg reduced striatal TH activity to 40‐50% of control, DA concentration to 38% of control, and TPH activity to 5520% of control. Intrastriatal injection of 16 pg of DHT reduced TH activity in the ipsilateral substantia nigra to 51% of control. Pretreatment with amfonelic acid, a potent DA uptake inhibitor, significantly reduced the effect of DHT on striatal and nigral TH activity and striatal DA concentration without affecting the DHT‐induced decrease in striatal TPH activity. Desmethylimipramine (5 and 25 mglkg) had no effect on the DHT‐induced decrease in striatal TH activity. Striatal choline acetyltransferase and glutamic acid decarboxylase activities were not decreased by 16 pg of DHT. The results indicate that DHT can alter dopaminergic function in the rat neostriatum through a direct effect of the drug on DA neurons.