ABSTRACT
The present study aimed to investigate the effects of sleep deprivation (SD) on the dose-dependent stimulant effect of ethanol (ETOH) on the open-field behavior of female and male mice. Sleep-deprived (48 h, multiple platforms method) or home-cage control female mice were treated with saline (SAL) or 1.4, 1.8 or 2.2g/kg ETOH 5 min before behavioral testing. ETOH produced a dose-dependent increase in open-field locomotor behavior. This locomotor stimulant effect did not reflect a general stimulation in motor activity, since it was accompanied by a simultaneous decrease in rearing frequency as well as by no modification in immobility duration. The effects of ETOH on these three behavioral parameters were specifically modified by SD: the locomotor stimulant effect was abolished, the rearing inhibitory effect was potentiated and the lack of effect on immobility was changed to increase in immobility. Similar results were obtained for male mice although the effects of SD had a lower magnitude. The present findings demonstrate that the acute effect of ETOH on mice's motor activity are behaviorally complex and can be specifically modulated by SD.
Subject(s)
Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Locomotion/drug effects , Sleep Deprivation/physiopathology , Analysis of Variance , Animals , Behavior, Animal/drug effects , Dose-Response Relationship, Drug , Exploratory Behavior/drug effects , Exploratory Behavior/physiology , Female , Freezing Reaction, Cataleptic/drug effects , Male , MiceABSTRACT
Recently we have described the antidyskinetic property of the GABA mimetic drugs valproic acid and topiramate on reserpine-induced oral dyskinesia. In this respect, oral dyskinesia has been associated with important neuropathologies. The present study investigates the effects of different doses of the GABA(A) agonist tetrahydroisoxazolopyridine (THIP), of the GABA(B) agonist baclofen as well as of the GABA(A) modulator diazepam on the manifestation of reserpine-induced orofacial dyskinesia. Male Wistar rats received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. Twenty-four hours later, animals were acutely treated with vehicle or THIP (2, 4 or 8 mg/kg), baclofen (1, 2 or 4 mg/kg) or diazepam (1, 2 or 4 mg/kg) and were observed for quantification of oral dyskinesia and open-field general activity. In order to verify the effects of these drugs per se on spontaneous oral movements, male Wistar rats were acutely treated with vehicle, 8 mg/kg THIP, 4 mg/kg baclofen or 4 mg/kg diazepam and observed for quantification of oral dyskinesia. The two highest doses of THIP or of baclofen abolished the manifestation of reserpine-induced oral dyskinesia while the lowest dose of baclofen attenuated it. Diazepam did not modify reserpine-induced oral dyskinesia at any dose tested. The highest doses of these drugs did not modify spontaneous oral movements. Reserpine-induced decrease in open-field general activity was not modified by any of the doses of THIP and diazepam or by the two lowest doses of baclofen. The highest dose of baclofen potentiated the increase in the duration of immobility induced by reserpine. These results reinforce the involvement of GABAergic hypofunction in the expression of oral dyskinesias, and support the potential therapeutic use of THIP and baclofen in the treatment of oral dyskinesias.
Subject(s)
Antipsychotic Agents/toxicity , Dyskinesia, Drug-Induced/drug therapy , GABA Agents/therapeutic use , Reserpine/toxicity , Analysis of Variance , Animals , Baclofen/therapeutic use , Behavior, Animal/drug effects , Diazepam/therapeutic use , Dose-Response Relationship, Drug , Drug Interactions , Dyskinesia, Drug-Induced/etiology , Immobility Response, Tonic/drug effects , Isoxazoles/therapeutic use , Locomotion/drug effects , Male , Rats , Rats, WistarABSTRACT
Recently, we have described the antidyskinetic property of the GABA mimetic drug valproic acid on reserpine-induced oral dyskinesia, an animal model that has been related to tardive as well as acute dyskinesias, which are associated with important neuropathologies. The present study investigates the effects of different doses of the GABA mimetic anticonvulsant topiramate on the manifestation of reserpine-induced orofacial dyskinesia. Female EPM-M1 mice received two injections of control solution or of 0.5 mg/kg reserpine separated by 48 h. Twenty-four hours after the second reserpine or control solution injection, animals were acutely treated with control solution or topiramate (1, 3, 10 or 30 mg/kg) and were observed for quantification of oral dyskinesia or general activity in an open-field. In order to verify the effects of topiramate per se on oral dyskinesia or general activity, female EPM-M1 mice were acutely treated with control solution or 1, 3, 10 or 30 mg/kg topiramate and observed for quantification of oral dyskinesia and general activity. The highest dose of topiramate completely abolished the manifestation of reserpine-induced oral dyskinesia whereas the doses of 3 and 10 mg/kg significantly attenuated it. None of the doses of the anticonvulsant modified spontaneous locomotion frequency or oral movements, whereas spontaneous rearing frequency was decreased by 3, 10 and 30 mg/kg topiramate. The highest dose of topiramate did not modify general activity in reserpine-treated mice. These results support the potential therapeutic use of topiramate in the treatment of oral dyskinesias.
