Rostrocaudal subregional differences in the response of enkephalin, dynorphin and substance P synthesis in rat nucleus accumbens to dopamine depletion.

Quantitative in situ hybridization histochemistry was used to examine the effects of unilateral 6-hydroxydopamine lesions of the ascending dopaminergic fibres on levels of mRNA encoding the neuropeptides enkephalin, dynorphin and substance P in subregions of the nucleus accumbens. The nucleus accumbens was divided into quadrants and changes in mRNA were measured along the rostrocaudal extent of the nucleus. Two weeks after the lesion an increase was found in enkephalin mRNA in the lesioned side compared to the non-lesioned side, whereas a decrease was observed for dynorphin and substance P mRNA. The changes in mRNA levels differed from quadrant to quadrant and were not uniformly distributed along the rostrocaudal axis. Both types of changes, i.e. increase and decrease, were much higher in rostral parts of the nucleus than in caudal parts, indicating regional differences in the effects of blockade of the dopaminergic neurotransmission. The lesion-induced increases and decreases in mRNA levels occurred in both the shell and the core subregions of the nucleus accumbens and were not specifically related to either of these areas. Factors are discussed that may contribute to the rostrocaudal gradient in the changes of enkephalin, substance P and dynorphin mRNA levels. On the basis of their afferent and efferent connections, the rostral and caudal parts of the nucleus accumbens are considered to be involved in different functions. The present results suggest that dopamine depletion may affect these functions in a differential manner.