Subchronic treatment with the neuroleptic-like peptide desenkephalin- γ-endorphin may decrease dopaminergic neurotransmission in the nucleus accumbens of rats

Abstract

In rats, subchronic administration of desenkephalin-γ-endorphin (DEγE) into the nucleus accumbens or subcutaneously for 10 days resulted in hypoactivity. Intra-accumbens administration caused a significant reduction in the nucleus accumbens tissue levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Systemic administration of DEγE decreased DOPAC and 5-hydroxyindoleacetic acid (5-HIAA) levels in nucleus accumbens tissue. Subchronic subcutaneous DEγE treatment reduced the basal release of [ 3H]DA from rat nucleus accumbens slices in vitro and the basal release of endogenous DA and DOPAC in vivo as assessed with on-line dialysis in the nucleus accumbens of freely moving rats. The DA agonist N, N-dipropyl-7-hydroxy-2-aminotetralin (DP-7-ATN) was equally effective in inhibiting [ 3H]DA release elicited by electrical stimulation from slices of subchronically DEγE and placebo treated rats. Administration of a small dose of apomorphine caused similar reductions of the in vivo release of DA and DOPAC in both placebo and DEγE treated rats. These results indicate that subchronic DEγE treatment may decrease dopaminergic neurotransmission in the nucleus accumbens. This effect is probably not due to alterations in the sensitivity of presynaptically located DA autoreceptors mediating DA release in vitro and in vivo.