Repeated treatment with imipramine, fluvoxamine and tranylcypromine decreases the number of escape failures by activating dopaminergic systems in a rat learned helplessness test

Chronic administration of antidepressants has been shown to reduce the numb er of escape failures in the rat learned helplessness test (LH). In the pre sent study we investigated the role of D-1, D-2 and D-3 receptors in mediat ing this effect. In our first series of experiments, we demonstrated that S KF38393, DI receptor agonist, in a dose of 2.5 mg/kg (i.p.) and quinpirole, D-2 receptor agonist in a dose of 0.5 mg/kg (i.p.), significantly decrease d the number of escape failures in LH, and these were reversed by SCH23390 (0.015 mg/kg), D-1 receptor antagonist, and by sulpiride (25 mg/kg), D-2 re ceptor antagonist, respectively. In contrast, 7-OH-DPAT, a D-3 receptor ago nist, in a dose of 10 mg/kg (i.p.) did not affect the number of escape fail ures in LH. In a second series of experiments, we showed that eight days of repeated treatment with imipramine (10 mg/kg, p.o.), fluvoxamine (1.25 mg/ kg, p.o.) and tranylcypromine (1.25 mg/kg, p.o.) significantly decreased th e number of escape failures in LH. The decrease in escape failures seen wit h use of imipramine and tranylcypromine was reversed by sulpiride in LH, bu t not by SCH23390. On the other hand, the effect of fluvoxamine was reverse d by both SCH23390 and sulpiride. These findings indicate that stimulation of D-1 and D-2 receptors decreased the number of escape failures in LH, res pectively. Thus, D-2 and/or D-1 receptors are probably involved in the decr eased number of escape failures in case of repeated treatment with antidepr essants in LH. (C) 2001 Elsevier Science Inc. All rights reserved.