Effects of muscarinic receptor agonists and antagonists on rat brain serotonergic activity

The effects of some muscarinic M1 and M2 receptor agonists and antagonists on rat brain serotonergic activity was assessed by noting their effects on the levels of 5-hydroxytryptamine (5-HT) and its major metabolite, 5-hydroxyindole acetic acid (5-HIAA), estimated by a high pressure-liquid chromatographic (HPLC) technique. The muscarinic M1 receptor agonists, arecholine and McN-A-343, and the M2 receptor agonists, gallamine and AF-DX 116, induced a dose-related decrease in the concentrations of both 5-HT and 5-HIAA. On the contrary, scopolamine and the selective M1 receptor antagonist, pirenzepine, increased the levels of the amine and its metabolite. The anti-cholinesterase agent, physostigmine, and the putative M2 receptor agonist, carbachol, induced a dose-related dual effect, with the smaller doses decreasing and the higher doses increasing 5-HT and 5-HIAA concentrations. The results indicate that an inverse relationship exists between the cholinergic and serotonergic neurotransmitter systems in the rat brain due to the likely presence of muscarinic heteroreceptors on serotonergic neurones. The data also indicates that though physostigmine and carbachol may function as M2 receptor agonists, they lose their receptor specificity on dose increment.