Interação dopamina-acetilcolina: ação de drogas que atuam nos sistemas dopaminérgico e colinérgico em cortex motor e corpo estriado de rato

Abstract

In the present paper, the interaction between dopaminergic and cholinergic systems in the rat motor córtex and striatum was studied. The foliowing drugs were used: mazindol and cocaine (indirect dopaminergic agonists), apomorphine (a non-selective dopaminergic agonist), pimozida and sulpirida (D2 antagonists), carbachol (muscarinic agonist of the M2-like subtype), and atropine (a non selective muscarinic antagonist). The interactions were investigated on the foliowing parameters: muscarinic (Ml plus M2-like, Ml or M2-like) and dopaminergic (Dl or D2-like) receptors densities; cyclic nucleotide leveis (cAMP and cGMP); acetylcholinesterase activity and behavior (open field and catalepsy). The results showed changes on the above parameters not only on the striatum but also on the rat motor córtex. Thus, in the motor córtex, mazindol and apomorphine increased the muscarinic receptor density. The effect was predominant on Ml-like receptors, and blocked by pimozida. Similarly, in the striatum, dopaminergic agonists (mazindol, apomorphine and cocaine) caused an increase in the muscarinic receptor density. A dopaminergic receptor upregulation was also observed after carbachol and atropine treatments, and this effect ocurred preferentially on Dl-like receptors. The cyclic nucleotide leveis were also altered. In the striatum, pimozida and carbachol increased significantly cAMP leveis only when administered in association. In the motor córtex, atropine decreased cAMP leveis, and this effect was not seen in the presence of mazindol. The observed decrease in AChE activity caused by mazindol was blocked by pimozida which did not cause any effect by itself. Mazindol also increased locomotor activity and the effect was potentiated by atropine. On the other hand, pimozida-induced catalepsy was not observed in the presence of carbachol. This work emphasizes dopaminergic versus muscarinic relationships which may be positive or negative depending on the parameters studied.