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

Tamanho da fonte: 
Lack of cross-tolerance between NOS inhibition and D2 receptor antagonist with metoclopramide in C57Bl mice
Nathalia B. Carrijo Oliveira, Marcela B. Echeverry, Aline Valéria Sousa-Santos, Aline Valéria Sousa-Santos

Última alteração: 2019-09-26


Past research indicates that the sub-chronic administration of NG-nitro-L-arginine (L-NOARG), a nitric oxide synthase (NOS) inhibitor, produces tolerance of haloperidol-induced catalepsy in Swiss mice and Clozapine in C57Bl mice, two antipsychotics with D2 receptor (D2R) antagonism. The present study aims to further investigate whether intermittent sub-chronic systemic administration of L-NOARG (LN) induces tolerance to the cataleptic effect of Metoclopramide (Met, Plasil®) in C57Bl mice, after sub-chronic administration for 5 consecutive days. Methods: Twenty male C57Bl6 mice received i.p. (i) LN (45 mg/kg) + Met (8 mg/kg) (n=6); (ii) Sal + Met (n=5); (iii) LN + Sal (n=6); (iv) Sal + Sal (n=3). The catalepsy (1, 3 and 5th days) and rotarod (2 and 4th days) test were recorded between 30-60 min after second injection. Two- way RM ANOVA with Duncan test was used. Our results show that sub-chronic administration of Met produced catalepsy devoid of tolerance; however it was observed that administration of LN, 30 min before Met, had an additive effect, and LN potentiated the cataleptic effect of Met [RM, F(1,16) = 24,563; P < 0.001, Duncan test P < 0.05]. All groups with Met showed decrease in the rotarod’s performance [RM, F(3,16) = 39,778, P < 0.001, Duncan test P < 0.05]. Overall, these results suggest that interference with the formation of NO mainly in D2R, with a drug acting as antagonists of high-affinity dopamine D2R, such as Met, could increase the cataleptic effect, categorized as extrapyramidal symptoms, commonly caused by antipsychotic drugs.