Stimulation of accumbal GABAB receptors inhibits delta1- and delta2-opioid receptor-mediated dopamine efflux in the nucleus accumbens of freely moving rats

The nucleus accumbens contains delta-opioid receptors that may decrease inhibitory neurotransmission. As GABA B receptors inhibit dopamine release, decrease in activation of GABA B receptors may be a mediator of delta-opioid receptor-induced accumbal dopamine efflux. If so, accumbal dopamine efflux induced by delta-opioid receptor activation should be suppressed by stimulating GABA B receptors. As delta-opioid receptors are further subdivided into delta1- and delta2-opioid receptors, we analysed the effects of the GABA B receptor agonist baclofen on delta1- and delta2-opioid receptor-mediated accumbal dopamine efflux in freely moving rats using in vivo microdialysis. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds show total amount administered (mol) during 25–50 min infusions. Baclofen (2.5 and 5.0 nmol), which did not alter basal dopamine levels, inhibited the delta1-opioid receptor agonist DPDPE (5.0 nmol)-induced dopamine efflux. Baclofen (2.5 and 5.0 nmol) also inhibited the delta2-opioid receptor agonist deltorphin II (25.0 nmol)-induced dopamine efflux. A low dose of the GABA B receptor antagonist 2-hydroxysaclofen (100.0 pmol), which failed to alter basal accumbal dopamine levels, counteracted the inhibitory effects of baclofen (5.0 nmol) on DPDPE (5.0 nmol)- and deltorphin II (25.0 nmol)-induced dopamine efflux. The present results show that reduction in accumbal GABA B receptor-mediated inhibition of accumbal dopaminergic activity facilitates activation of delta1- and delta2-opioid receptor-induced increases in accumbal dopamine efflux. This study suggests that activation of delta1- and delta2-opioid receptors on the cell bodies and/or terminals of accumbal GABAergic interneurons inhibits GABA release and, accordingly, decreases GABA B receptor-mediated inhibition of dopaminergic terminals, resulting in enhanced accumbal dopamine efflux.