Efeitos da administração crônica de Nimesulida e/ou Haloperidol sobre os parâmetros bioquímicos e comportamentais em camundongos.

Abstract

Schizophrenia is a severe mental disorder a chronic, debilitating condition that affects about 1% of the world population, has serious consequences for patients and their families and with important economic impact on the public health system. The treatment of schizophrenia requires long-term administration of antipsychotic drugs including haloperidol, a typical antipsychotic, is among the most used. However, its side effects limit its use, highlighting the extrapyramidal effects. Its pharmacological effects, both as therapeutic adverse are the result of antagonism of dopamine D2-type mesolimbic and possibly mesocorticais. Extrapyramidal effects also result of this antagonism, especially in striatum, mesolimbic pathway-nigrostriatal. In this context, the objective of this study was to investigate the possible reversal of the adverse effects of antipsychotic haloperidol by nonsteroidal anti-inflammatory drug nimesulide, and analyze the possible involvement of the enzyme AChE (Acetylcholinesterase) in the action of haloperidol and possible reversal induced by nimesulide. Male mice were used, initially divided into 4 groups (N = 8-10/group) and treated once a week for 11 weeks with: G1- Saline (NaCl 0.9%), G2- Tween 1%, G3-Haloperidol 7 mg/kg and G4- Haloperidol 14 mg/kg. From the 7th week, the groups were subdivided for additional treatment with anti-inflammatory drug Nimesulide once daily until the 11th week (last), forming seven groups: G1A- Salina X Salina, G1B- Salina X Nimesulide, G2A- Tween 1% X Salina, G3A- Haloperidol 7mg/kg X Salina, G3B- Haloperidol 7 mg/kg X Nimesulide, G4A- Haloperidol 14 mg/kg X Salina, G4B- Haloperidol 14 mg/kg X Nimesulide. Tests conducted in vivo, demonstrated a reduction in the number of dung in all groups compared to control G1A, which was not reversed by nimesulide, reduced spontaneous locomotor activity in groups G3A, and G4A G4B and increased cataleptic effect in groups G3A and G4A and reversal of these effects by nimesulide in Group G3B. However, this reversal does not occur via alteration in the activities of AChE hippocampal and striatal since, regardless of treatment, no significant alteration of this enzyme. Already in the prefrontal cortex, haloperidol produced an increase in enzyme activity in groups G3A, and G4A G4B, and consequent decreased cholinergic function, and this effect was reversed by nimesulide (Group G3B). The results of this study suggest a possible influence of Nimesulide in cholinergic activity and the reversal of extrapyramidal effects caused by haloperidol.