ABSTRACT
The purpose of the present work was to study the dose-effect relationship of the antidepressant amitriptyline on inhibitory avoidance in male and female mice. Subjects received physiological saline or 2.5, 5, 10 or 20 mg/kg of amitriptyline hydrochloride 30 min before the training phase, and were subjected to the test phase 24 h later. Results showed a clear impairing effect of amitriptyline on inhibitory avoidance in both male and female mice, and that the effect is dose-dependent.
Subject(s)
Amitriptyline/pharmacology , Avoidance Learning/drug effects , Amitriptyline/administration & dosage , Animals , Depression, Chemical , Dose-Response Relationship, Drug , Female , Male , Mice , Random Allocation , Reaction Time/drug effectsABSTRACT
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.
Subject(s)
Amitriptyline/adverse effects , Antidepressive Agents, Tricyclic/adverse effects , Cholinergic Agonists/pharmacology , Learning Disabilities/drug therapy , Oxotremorine/pharmacology , Physostigmine/pharmacology , Amitriptyline/administration & dosage , Animals , Antidepressive Agents, Tricyclic/administration & dosage , Avoidance Learning/drug effects , Cholinergic Agonists/administration & dosage , Female , Learning Disabilities/chemically induced , Male , Mice , Mice, Inbred Strains , Oxotremorine/administration & dosage , Physostigmine/administration & dosage , Random Allocation , Sex Characteristics , Time FactorsABSTRACT
The purpose of the present work was to study the dose-effect relationship of the antidepressant amitriptyline on inhibitory avoidance in male and female mice. Subjects received physiological saline or 2.5, 5, 10 or 20 mg/kg of amitriptyline hydrochloride 30 min before the training phase, and were subjected to the test phase 24 h later. Results showed a clear impairing effect of amitriptyline on inhibitory avoidance in both male and female mice, and that the effect is dose-dependent (AU)
El propósito del presente trabajo fue estudiar la relación dosis-efecto del antidepresivo amitriptilina sobre la evitación inhibitoria en ratones machos y hembras. Los sujetos recibieron suero salino o 2.5, 5, 10 ó 20 mg/kg de clorhidrato de amitriptilina 30 min antes de la fase de entrenamiento, y fueron sometidos a la fase de test 24 h más tarde. Los resultados mostraron un claro efecto deteriorante de la amitriptilina sobre la evitación inhibitoria tanto en los ratones machos como en las hembras, y que el efecto es dependiente de dosis (AU)
Subject(s)
Animals , Male , Female , Mice , Amitriptyline/metabolism , Amitriptyline/therapeutic use , Dose-Response Relationship, Drug , Antidepressive Agents/metabolism , Antidepressive Agents/therapeutic use , Serum , Latency Period, PsychologicalABSTRACT
The effects of chronic administration of fluoxetine (20 mg/kg/day i.p.) on a one-trial step-through inhibitory avoidance task were investigated in male and female CD1 mice. In Experiment 1, treatment was administered for 21 days before the training session, whereas in Experiment 2, other subjects were subjected to the same treatment starting 24 h after the training session. The comparison of test versus training latencies showed memory deterioration with pre-training administration of fluoxetine (Experiment 1), which affected males but not females. Sex differences in this task were also observed in Experiment 1, with females showing a better performance. Sex differences were evident in controls as well as in treated animals. The locomotor activity of the animals was also tested in Experiment 1. Due to the absence of sex differences in the drug effects on this measure, the sex differences in the effects of fluoxetine on inhibitory avoidance were hardly attributable to non specific effects on locomotor activity. The lack of effect of post-training administration of fluoxetine (Experiment 2) constitutes additional support of the idea that the observed effect on inhibitory avoidance in Experiment 1 is specifically related to learning and memory.