title: Effects of oxotremorine and physostigmine on the inhibitory avoidance impairment produced by amitriptyline in male and female mice.
abstract: We have previously observed that amitriptyline and other antidepressants produce impairing effects on inhibitory avoidance (also called passive avoidance) in mice of both sexes. In the present study we investigated the involvement of the cholinergic system in the inhibitory avoidance impairment produced by acute amitriptyline in male and female CD1 mice. For this purpose, the effects on said task of acute i.p. administration of several doses of amitriptyline, either alone or in combination with the cholinergic agonists oxotremorine and physostigmine, were evaluated. Pre-training administration of 5, 7.5, 10 or 15 mg/kg of amitriptyline produced a significant impairment of inhibitory avoidance in both males and females. When oxotremorine (0.05 or 0.1 mg/kg) was co-administered with amitriptyline, the antidepressant's impairing effect was partially counteracted, although inhibitory avoidance learning was not significant. Physostigmine (0.15, 0.3 or 0.6 mg/kg) counteracted the impairment produced by amitriptyline, as mice treated with both drugs exhibited inhibitory avoidance learning. These results show that the inhibitory avoidance impairment produced by amitriptyline in male and female mice is mediated, at least partially, by the cholinergic system.
authors.affiliation: Department of Psychobiology, University of Valencia, Valencia, Spain. santiago.monleon@uv.es
authors.forename: Santiago
authors.initials: S
authors.lastname: Monleón
authors.forename: Adoración
authors.initials: A
authors.lastname: Urquiza
authors.forename: Concepción
authors.initials: C
authors.lastname: Vinader-Caerols
authors.forename: Andrés
authors.initials: A
authors.lastname: Parra
mesh_terms: D000639:Amitriptyline / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000009:adverse effects*; D001362:Avoidance Learning / Q000187:drug effects; D018679:Cholinergic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010095:Oxotremorine / Q000008:administration & dosage / Q000494:pharmacology*; D010830:Physostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D018679:Cholinergic Agonists; D000639:Amitriptyline; D010095:Oxotremorine; D010830:Physostigmine