Early changes in neuropeptide mRNA expression in the striatum following reserpine treatment

Chronic dopamine depletion produces neurochemical changes within the striat um as well as enhanced behavioral and metabolic responses to dopamine agoni sts, Changes in striatal neuropeptides have been consistently described, in cluding increased expression of preproenkephalin mRNA and decreased express ion of preprotachykinin and prodynorphin mRNA Acute dopamine depletion foll owing treatment with reserpine also produces enhanced behavioral and metabo lic responses to agonist treatment which develop rapidly. In the present st udy, we used in situ hybridization histochemistry to investigate whether ac ute neurochemical changes occur following reserpine treatment. We evaluated neuropeptide mRNA expression in the striatum and nucleus accumbens at seve ral time points from 6 to 120 h following single doses of reserpine and AMP T. The aim of these studies was to determine if changes in neuropeptide mRN A expression occur following acute dopamine depletion and whether such chan ges are specific to the striatum. Changes in striatal neuropeptide mRNA exp ression developed rapidly. Preproenkephalin mRNA expression by striatopalli dal neurons was unchanged at 48 h, but increased by 44% at 120 h. Preprotac hykinin mRNA expression in striatonigral neurons was increased at 6 h and t hen fell, with a maximal decrease of 45% at 48 h and partial recovery by 12 0 h, Prodynorphin mRNA expression was unchanged. Expression of preproenkeph alin and preprotachykinin mRNA was also examined in subregions of the stria tum and the nucleus accumbens. Expression of preproenkephalin mRNA was unif orm in the striatum and higher in the core than the shell of the nucleus ac cumbens, Preprotachykinin mRNA expression in the striatum was higher in the lateral quadrants and was higher in the shell than in the core of the nucl eus accumbens. The changes in neuropeptide mRNA following treatment with re serpine were only found in the striatum, These data provide further evidenc e for early alterations in neuronal function in the striatum following acut e dopamine depletion and suggest that neuropeptide expression by striatonig ral neurons may be more rapidly regulated in response to changes in dopamin e levels. (C) 2000 Academie Press.