Alpha 2 and beta-adrenoceptor agonists modulate [3H]dopamine release from rat nucleus accumbens slices: implications for research into depression.

The modulatory effects of noradrenergic agonists on the 25 mM K+-induced release of [3H]dopamine (3H-DA) from rat brain nucleus accumbens slices was investigated, using a superfusion technique. The K+-induced release of 3H-DA was Ca2+ dependent, significantly enhanced (25-32%; p less than 0.02) by the beta-adrenoceptor agonist isoproterenol (10 microM), and significantly decreased (13-25%; p less than 0.05) by the alpha 2-adrenoceptor agonist clonidine (10 microM). At these concentrations neither drug affected basal release of 3H-DA. Clonidine (100 microM) increased the basal release of 3H-DA, while decreasing the K+-induced release by 19% (p less than 0.01). The inclusion of desipramine in the incubation medium, to prevent accumulation of 3H-DA into noradrenergic neurons, did not alter the inhibitory effect of clonidine (10 microM) on 3H-DA release. This study provides direct evidence that noradrenergic neurons can modulate dopaminergic neurotransmission in the mesolimbic system.