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JM O'Donnell, S Frith and J Wilkins
Department of Pharmacology and Therapeutics, Louisiana State University Medical School, Shreveport.
Central (i.c.v.) but not peripheral (i.p.) administration of isoproterenol reduced response rates and increased reinforcement rates of rats under a differential-reinforcement-of-low-response-rate 72-sec schedule in a dose-dependent manner. This effect of centrally administered isoproterenol was similar to effects produced by administration of proven antidepressant drugs. Propranolol antagonized the effect of centrally administered isoproterenol, suggesting that the antidepressant-like effect of this agonist was mediated by beta adrenergic receptors. In addition, both the beta-1 selective antagonist betaxolol and the beta-2 selective antagonist ICI 118,551 antagonized the effect of centrally administered isoproterenol in a dose-dependent manner. These antagonists exhibited similar potency, suggesting that both beta-1 and beta-2 adrenergic receptors were involved in the mediation of the antidepressant-like effect of centrally administered isoproterenol. In rats with down-regulated beta-2 adrenergic receptors, produced by repeated treatment with clenbuterol, isoproterenol still reduced response rates and increased reinforcement rates of rats under the differential-reinforcement-of-low-response-rate schedule. By contrast, the antidepressant-like effect of the beta-2 adrenergic agonist clenbuterol was attenuated by down-regulation of beta-2 adrenergic receptors. The present results indicate that stimulation of central beta adrenergic receptors by intraventricular administration of isoproterenol produces behavioral changes similar to those observed after administration of proven antidepressant drugs. Both beta-1 and beta-2 adrenergic receptors appear to mediate the antidepressant-like effect of isoproterenol.
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