Effect of chronic desipramine treatment on adrenoceptor modulation of [3H]dopamine release from rat nucleus accumbens slices.
The effects of alpha 2- and beta-adrenoceptor agonists on the 25 mM K+-induced release of [3H]dopamine [( 3H]DA) from the 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 Ca2+ dependent and to be enhanced 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 alpha 2-adrenoceptor agonist, clonidine (10 microM; 89 +/- 2.4% of control values; P less than 0.002), and significantly enhanced by the beta-adrenoceptor agonist, isoproterenol (1 and 10 microM; 122 +/- 4.3 and 171 +/- 2.9% of control values, P less than 0.002 and P less than 0.001, respectively). The basal release of [3H]DA was strongly enhanced by 10 microM but not 1 microM 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 alpha 2-adrenoceptor-mediated inhibition of [3H]DA release, while the beta-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.
D000818:Animals; D002118:Calcium / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012686:Septal Nuclei / Q000378:metabolism*
D011941:Receptors, Adrenergic; D007545:Isoproterenol; D003000:Clonidine; D002118:Calcium; D003891:Desipramine; D004298:Dopamine