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 number of escape failures in the rat learned helplessness test (LH). In the present study we investigated the role of D1, D2 and D3 receptors in mediating this effect. In our first series of experiments, we demonstrated that SKF38393, D1 receptor agonist, in a dose of 2.5 mg/kg (i.p.) and quinpirole, D2 receptor agonist in a dose of 0.5 mg/kg (i.p.), significantly decreased the number of escape failures in LH, and these were reversed by SCH23390 (0.015 mg/kg), D1 receptor antagonist, and by sulpiride (25 mg/kg), D2 receptor antagonist, respectively. In contrast, 7-OH-DPAT, a D3 receptor agonist, in a dose of 10 mg/kg (i.p.) did not affect the number of escape failures 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 the number of escape failures in LH. The decrease in escape failures seen with use of imipramine and tranylcypromine was reversed by sulpiride in LH, but not by SCH23390. On the other hand, the effect of fluvoxamine was reversed by both SCH23390 and sulpiride. These findings indicate that stimulation of D1 and D2 receptors decreased the number of escape failures in LH, respectively. Thus, D2 and/or D1 receptors are probably involved in the decreased number of escape failures in case of repeated treatment with antidepressants in LH.
Takamori
K
K
CNS Diseases Research, Laboratory-1, Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd., Ohmiya, Saitama, Japan. s17525@ccm.taisho.co.jp
Yoshida
S
S
Okuyama
S
S
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D016666:Fluvoxamine / Q000494:pharmacology*; D006380:Helplessness, Learned; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology*
D000928:Antidepressive Agents; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D014191:Tranylcypromine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D016666:Fluvoxamine; D007099:Imipramine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin