Effects of baclofen on reserpine-induced vacuous chewing movements in mice.
We have described that GABA mimetic drugs present the ability to inhibit the expression of reserpine-induced oral movements. In this respect, oral movements is associated with important neuropathologies. This study investigates the effects of an acute or a repeated treatment of different doses of the GABA(B) agonist baclofen, as well as withdrawal from these treatments, on the development and/or expression of reserpine-induced vacuous chewing movements (VCM). Male mice received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. In the first experiment, 24h later, animals were acutely treated with vehicle or baclofen (1, 2 or 4 mg/kg). In the second experiment, animals were treated with vehicle or baclofen (1 or 4 mg/kg) for four consecutive days receiving a concomitant injection of 1mg/kg reserpine (or vehicle) on Days 2 and 4. Twenty-four hours later, animals received vehicle or baclofen. Thirty minutes after the last injection, they were observed for quantification of VCM and open-field general activity. The acute administration of all the doses of baclofen abolished the manifestation of reserpine-induced VCM. Repeated treatment with 1mg/kg baclofen induced tolerance to the ability of an acute injection of this dose to reduce VCM. Treatment with baclofen (4 mg/kg) did not modify spontaneous VCM. Acute administration of the highest dose induced a decrease in general motor activity and a potentiation of the reserpine-induced decrease in general activity. These results reinforce the involvement of GABAergic hypofunction in the expression of oral movements and suggest that a repeated treatment with baclofen induces compensatory changes in GABAergic transmission that can attenuate its acute property to decrease VCM.
Castro
Juliana P M V
JP
Department of Pharmacology, Escola Paulista de Medicina/UNIFESP, São Paulo, Brazil.
Frussa-Filho
Roberto
R
Fukushiro
Daniela F
DF
Silva
Regina H
RH
Medrano
Wladimir A
WA
Ribeiro
Rosana de A
Rde A
Abílio
Vanessa C
VC
D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000037:antagonists & inhibitors; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000503:physiopathology*; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000378:metabolism; D012110:Reserpine / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D012110:Reserpine; D001418:Baclofen