Involvement of dopamine D1 receptors and alpha1-adrenoceptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test.
It has been reported that chlorpheniramine, a classical antihistamine, has antidepressant-like effects in animal models of depression. In this study, we examined the involvement of dopaminergic (dopamine D(1) and dopamine D(2) receptors), noradrenergic (alpha(1)- and beta-adrenoceptors) and serotonergic (5-HT(1A) and 5-HT(2) receptors) receptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test. We also investigated the involvement of these monoamine receptors in the antidepressant-like effect of imipramine for comparison with the mechanisms of the effect of chlorpheniramine. Both imipramine and chlorpheniramine significantly reduced the duration of immobility in the tail suspension test without affecting spontaneous locomotor activity in mice. The anti-immobility effect of imipramine (30 mg/kg, i.p.) was significantly antagonized by the selective dopamine D(1) receptor antagonist SCH23390 but not by the other receptor antagonists. In contrast, the anti-immobility effect of chlorpheniramine was significantly inhibited by SCH23390 and the selective alpha(1)-adrenoceptor antagonist prazosin, but not by the other receptor antagonists. In conclusion, these results suggest that chlorpheniramine exerts an antidepressant-like effect in the mouse tail suspension test that is mediated by at least the activation of dopamine D(1) receptors and alpha(1)-adrenoceptors. In addition, the antidepressant-like effect of chlorpheniramine may be induced by several mechanisms that are different from those involved in the antidepressant-like effect of imipramine.
Hirano
Shoko
S
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan.
Miyata
Shigeo
S
Onodera
Kenji
K
Kamei
Junzo
J
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019417:Hindlimb Suspension / Q000502:physiology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D006634:Histamine H1 Antagonists; D018340:Receptors, Adrenergic, alpha-1; D017447:Receptors, Dopamine D1; D002744:Chlorpheniramine; D007099:Imipramine; D011224:Prazosin