Effects of muscarinic receptor agonists and antagonists on dopamine-mediated behavioural paradigms.

The effects of some muscarinic M1 and M2 receptor agonists and antagonists on two dopamine-mediated behavioural paradigms, namely post-swim grooming response and apormorphine-induced climbing behaviour, was investigated in mice. The M1 agonists and M2 receptor antagonists attenuated both paradigms, whereas the M1 receptor antagonists and M2 receptor agonists facilitated both behaviours. However, carbachol and physostigmine, exhibited a similar dose-dependent dual effect with the lower doses augmenting and the higher doses inhibiting both the behaviours, suggesting that the M2 agonist receptor specificity is lost on dose increment. The findings indicate that the central cholinergic muscarinic heteroreceptors, like the other muscarinic receptors, are functionally divisible into M1 and M2 receptor subtypes in their modulation of dopaminergic activity.