Sistema de Submissão de Resumos, IX ENCONTRO DE INICIAÇÃO CIENTÍFICA - 2019

Tamanho da fonte: 
Metoclopramide induced-tardive dystonia and extrapyramidal side effects by chronic administration in C57Bl6 mice
Gabriel B. de Lima Castilho, Marcela B. Echeverry, Victor Ricardo Cândido Torres Silva, Victor Ricardo Cândido Torres Silva

Última alteração: 2019-09-26


Rationale: High and sustained D2 occupancy rates by neuroleptics increases dramatically the Extrapyramidal side effects (EPS). However, movement disorders induced by long-term Metoclopramide (Met, Plasil®) administration, with cumulative dosage, still remains unknown. Objective: The present study aims to further investigate whether catalepsy, an extrapyramidal side effect associated with antipsychotics is decrease with chronic administration of Met (phase 1), and to determine the differential and long-lasting changes in FosB distribution in the striatum and nucleus accumbens (NAc), associated with antipsychotic-induced extrapyramidal side effects (phase 2). Methods: Male C57Bl/6 mice at 9 weeks of age received daily injections i.p. of (i) Met, 5 mg/kg for 3 weeks and 8 mg/kg in the last 4th week), (ii) Met, 8 mg/kg for 3 weeks and 25 g/kg in the last 4th week), (iii) Saline (vol 10ml/kg), for an 4-week treatment period. Results: Met 8 and 25 mg/kg produced catalepsy, with disabilities in performance on the rota-rod test. For the same doses, hyperkinetic movement disorders were observed and an excessive teeth grinding (bruxism), likely an Oromandibular dystonia (OMD) was observed in 3 animals, just a few minutes later Met administration, as of the third week. Conclusion: This study provides evidence that even Met give rise to EPS frequently associated with a cumulative dosage of typical neuroleptics such as Hal and OMD can also be observed.