title: Involvement of α1B-adrenoceptors in the anti-immobility effect of imipramine in the tail suspension test.
abstract: Imipramine is a tricyclic antidepressant inhibitor of norepinephrine and serotonin neuronal reuptake. The roles of specific α1-adrenoceptor subtypes that might be targeted by the increased synaptic levels of noradrenaline induced by imipramine are not well understood. This study investigates the α1-adrenoceptor subtypes involved in the anti-immobility effect of imipramine in the mouse tail suspension test. The anti-immobility effect of imipramine (32mg/kg, i.p.) was significantly antagonised by the non-subtype-selective α1-adrenoceptor antagonist prazosin (0.5 and 1.0mg/kg, i.p.). Neither the selective α1A-adrenoceptor antagonist 5-methyl-3-[3-[3-[4-[2-(2,2,2,-trifluroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H,3H)-pyrimidinedione (RS-100329, 0.5 and 1.0mg/kg) nor the selective α1D-adrenoceptor antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride, (BMY-7378, up to 1.0mg/kg, i.p.) affected the anti-immobility effect of imipramine. However, the anti-immobility effect of imipramine was significantly antagonised by the selective α1B-adrenoceptor antagonist (2S)-4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-2-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperazinecarboxylate (L-765,314). In addition, mice treated only with RS-100329 or BMY-7378, but not with L-765,314, showed reduced immobility times in comparison to mice treated with vehicle. These results indicate that the selective antagonism of α1A- and α1D-adrenoceptors results in antidepressant-like effects and that the α1B-subtype is the main target for the increased levels of noradrenaline caused by imipramine.
authors.affiliation: Department of Pharmacology, Instituto de Biociências, UNESP, Botucatu, SP, Brazil.
authors.forename: Carlos Alberto S
authors.initials: CA
authors.lastname: Ribeiro
authors.affiliation: Department of Pharmacology, Instituto de Biociências, UNESP, Botucatu, SP, Brazil. Electronic address: aspupo@ibb.unesp.br.
authors.forename: André S
authors.initials: AS
authors.lastname: Pupo
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D019417:Hindlimb Suspension / Q000009:adverse effects*; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D007099:Imipramine
keywords: Imipramine; Tail suspension test; Tricyclic antidepressants; α(1)-Adrenoceptors; α(1B)-Adrenoceptor