Involvement of alpha(1B)-adrenoceptors in the anti-immobility effect of imipramine in the tail suspension test

Imipramine is a tricyclic antidepressant inhibitor of norepinephrine and serotonin neuronal reuptake. The roles of specific alpha(1)-adrenoceptor subtypes that might be targeted by the increased synaptic levels of noradrenaline induced by imipramine are not well understood. This study investigates the alpha(1)-adrenoceptor subtypes involved in the anti-immobility effect of imipramine in the mouse tail suspension test. The antiimmobility effect of imipramine (32 mg/kg, i.p.) was significantly antagonised by the non-subtype-selective alpha(1)-adrenoceptor antagonist prazosin (0.5 and 1.0 mg/kg, i.p.). Neither the selective alpha(1A)-adrenoceptor antagonist 5-methyl-3-[3-[3-[4-[2-(2,2,2,-trifluroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1H,3H)-pyrimidineclione (RS-100329, 0.5 and 1.0 mg/kg) nor the selective alpha(1D)-adrenoceptor antagonist 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride, (BMY-7378, up to 1.0 mg/kg, i.p.) affected the anti-immobility effect of imipramine. However, the anti-immobility effect of imipramine was significantly antagonised by the selective alpha(1B)-adrenoceptor antagonist (2S)-4-(4-amino-6,7-dimethoxy-2quinazoliny1)-2-[[(1,1-dimethylethyl)aminolcarbonyl]-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 alpha(1A)- and alpha(1D)- adrenoceptors results in antidepressant-like effects and that the am-subtype is the main target for the increased levels of noradrenaline caused by imipramine. (C) 2015 Elsevier B.V. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP