Early Changes in Neuropeptide mRNA Expression in the Striatum Following Reserpine Treatment

Abstract

Chronic dopamine depletion produces neurochemical changes within the striatum as well as enhanced behavioral and metabolic responses to dopamine agonists. Changes in striatal neuropeptides have been consistently described, including increased expression of preproenkephalin mRNA and decreased expression of preprotachykinin and prodynorphin mRNA. Acute dopamine depletion following treatment with reserpine also produces enhanced behavioral and metabolic responses to agonist treatment which develop rapidly. In the present study, we used in situ hybridization histochemistry to investigate whether acute neurochemical changes occur following reserpine treatment. We evaluated neuropeptide mRNA expression in the striatum and nucleus accumbens at several time points from 6 to 120 h following single doses of reserpine and AMPT. The aim of these studies was to determine if changes in neuropeptide mRNA expression occur following acute dopamine depletion and whether such changes are specific to the striatum. Changes in striatal neuropeptide mRNA expression developed rapidly. Preproenkephalin mRNA expression by striatopallidal neurons was unchanged at 48 h, but increased by 44% at 120 h. Preprotachykinin mRNA expression in striatonigral neurons was increased at 6 h and then fell, with a maximal decrease of 45% at 48 h and partial recovery by 120 h. Prodynorphin mRNA expression was unchanged. Expression of preproenkephalin and preprotachykinin mRNA was also examined in subregions of the striatum and the nucleus accumbens. Expression of preproenkephalin mRNA was uniform in the striatum and higher in the core than the shell of the nucleus accumbens. Preprotachykinin mRNA expression in the striatum was higher in the lateral quadrants and was higher in the shell than in the core of the nucleus accumbens. The changes in neuropeptide mRNA following treatment with reserpine were only found in the striatum. These data provide further evidence for early alterations in neuronal function in the striatum following acute dopamine depletion and suggest that neuropeptide expression by striatonigral neurons may be more rapidly regulated in response to changes in dopamine levels.