Effect of chronic desipramine treatment on adrenoceptor modulation of [ 3H]dopamine release from rat nucleus accumbens slices

Abstract

The effects of α 2- and β-adrenoceptor agonists on the 25 mM K +-induced release of [ 3H]dopamine ([ 3H]DA from nucleus accumbens slices of chronic desipramine (DMI)- and saline-treated rats were investigated using a superfusion technique. The K +-induced release of [ 3H]DA from nucleus accumbens slices was shown to be Ca 2+-dependent by ascorbic acid. In experiments with isoproterenol, ascorbic acid was added to the superfusion media in order to prevent the otherwise rapid oxidation of the drug. The K +-induced release of [ 3H]DA from nucleus accumbens slices of saline-treated rats was significantly decreased by the α 2-adrenoceptor agonist, clonidine(10 μM; 89 ± 2.4%of control values; P < 0.002), and significantly enhanced by the β-adrenoceptor agonist, isoproterenol(1 and 10 μM; 122 ± 4.3and171 ± 2.9%of control values, P < 0.002andP < 0.001, respectively). The basal release of [ 3H]DA was strongly enhanced by 10 μM but not 1 μM isoproterenol. Chronic DMI pretreatment (10 mg/kg i.p. for 28 days) did not significantly alter the K +-induced release of [ 3H]DA. Chronic DMI treatment attenuated the α-adrenoceptor-mediated inhibition of [ 3H]DA release, while the β-adrenoceptor-mediated stimulation remained unchanged. The net effect of chronic DMI treatment therefore would appear to be a facilitation of dopaminergic neurotransmission in the mesolimbic system. This is consistent with behavioural evidence which suggests that the function of the mesolimbic dopaminergic reward system is facilitated by chronic treatment with antidepressant drugs.