ANÁLISE DA INTERAÇÃO ENTRE ACETILCOLINA E DOPAMINA SOBRE O COMPORTAMENTO MOTOR EM UM MODELO ANIMAL DA DOENÇA DE PARKINSON.

Abstract

The objective of this study was to evaluate the effect of the muscarinic M4 acetylcholine receptor antagonist, PCS1055 dihydrochloride, on catalepsy and changes in locomotor behavior in mice, induced by haloperidol, a dopamine receptor antagonist, and by L-NOARG, a nitric oxide synthase inhibitor. Two experiments were conducted with six groups, each containing eight male Swiss mice weighing between 20-30g. In Experiment I, the animals received an intraperitoneal (i.p.) injection of saline or haloperidol (2 mg/kg), followed by i.p. administration of saline or PCS1055 dihydrochloride (2.5 and 10 mg/kg) after 30 minutes. In Experiment II, the animals received an i.p. injection of saline or L-NOARG (40 mg/kg), followed by i.p. administration of saline or PCS1055 dihydrochloride (2.5 and 10 mg/kg) after 30 minutes. At 30, 60, and 90 minutes after drug administration, the animals underwent the bar catalepsy test, and after 60 minutes, the Open Field test. Analysis of the effect of group, time, and the interaction between factors on catalepsy duration was performed using two-way repeated-measures ANOVA, followed by Tukey's post hoc test. Comparison among experimental groups regarding the amount of horizontal and vertical exploratory behaviors was conducted using one-way ANOVA, followed by Tukey's post hoc test. In Experiment I, animals that received haloperidol showed a longer catalepsy duration compared to those that received saline as the first drug (Tukey post hoc test, p<0.05). Additionally, at the 90-minute time point, PCS1055 dihydrochloride, at both doses, potentiated the cataleptic effect of haloperidol. PCS1055 dihydrochloride also intensified the motor changes induced by haloperidol, specifically in terms of the horizontal exploration of the animals (Tukey post hoc test, p<0.05). In Experiment II, L-NOARG induced catalepsy and locomotor changes in the animals (Tukey post hoc test, p<0.05), which were not reversed by the administration of PCS1055 dihydrochloride at any analyzed time points in the catalepsy test and the Open Field test. Additionally, PCS1055 dihydrochloride at a dose of 2.5 mg/kg alone (Saline + PCS1055 dihydrochloride) led to hypolocomotion and reduced vertical exploration in the Open Field test (Tukey post hoc test, p<0.05). Thus, PCS1055 had an effect completely opposite to that expected in terms of reversing catalepsy and changes in exploratory behavior in the Open Field test induced by both haloperidol and L-NOARG. Descriptors: basal ganglia, acetylcholine receptors, catalepsy, dopamine.