title: A lack of α1A-adrenergic receptor-mediated antidepressant-like effects of S-(+)-niguldipine and B8805-033 in the forced swim test.
abstract: The α1-adrenergic receptors (α1-ARs), which belong to a G protein-coupled receptor family, consist of three highly homologous subtypes known as α1A-ARs, α1B-ARs, and α1D-ARs. Our previous findings suggested that α1A-ARs are an important target for imipramine and electroconvulsive therapy. The current study sought to evaluate whether S-(+)-niguldipine and B8805-033, two selective antagonists of α1A-ARs, can evoke antidepressant-like effects in the forced swim test in rats. Both compounds were administered at three time points (24, 5, and 1 h before testing), and the effects of three doses (2, 5, and 10 mg/kg) of each compound were investigated. S-(+)-Niguldipine produced no antidepressant-like effects other than a 14% reduction in immobility time at the highest dose. Although B8805-033 at a dose of 2 mg/kg did not influence the rats' behavior, higher B8805-033 doses (5 and 10 mg/kg) produced significant reductions in immobility time (approximately 42 and 44% vs. controls, respectively; P<0.01). However, this effect was abolished by the concomitant administration of WAY100135, a serotonin receptor antagonist, suggesting that the observed antidepressant-like effects of B8805-033 are unrelated to α1A-ARs. Nevertheless, given the current dearth of selective α1A-AR agonists, the question of whether this particular subtype could be involved in antidepressant therapy mechanisms remains unresolved.
authors.affiliation: Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kreiner
authors.forename: Adam
authors.initials: A
authors.lastname: Roman
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zelek-Molik
authors.forename: Marta
authors.initials: M
authors.lastname: Kowalska
authors.forename: Irena
authors.initials: I
authors.lastname: Nalepa
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004147:Dioxins / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011744:Pyrimidinones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D013550:Swimming; D013997:Time Factors
chemical_list: C438684:1,3,5-trimethyl-6-((3-(4-((2,3-dihydro-2-hydroxymethyl)-1,4-benzodioxin-5-yl)-1-piperazinyl)propyl)amino)-2,4(1H,3H)-pirymidinedione; D058668:Adrenergic alpha-1 Receptor Antagonists; D000928:Antidepressive Agents; D004095:Dihydropyridines; D004147:Dioxins; D010879:Piperazines; D011744:Pyrimidinones; D018340:Receptors, Adrenergic, alpha-1; C081293:WAY 100135; C054074:niguldipine