Barnes_1991_Eur.J.Pharmacol_195_233

The in vivo central effects of a range of full and partial muscarinic receptor agonists have been investigated on hippocampal theta rhythm and blood pressure. In the isoflurane-anaesthetised rat, pretreated with N-methylscopolamine, i.v. administration of arecoline, oxotremorine, arecaidine propargyl ester, aceclidine and pilocarpine produced dose-dependent increases in the frequency of hippocampal theta rhythm and blood pressure, with an order of potency of arecoline = oxotremorine = arecaidine propargyl ester greater than aceclidine greater than or equal to pilocarpine. To increase theta wave frequency, pilocarpine showed a low maximum response and possessed antagonist activity against arecoline, indicating that pilocarpine was acting as a partial agonist. AF102B failed to alter blood pressure or theta rhythm. Intraventricular injections of scopolamine and the M1 receptor-selective antagonist, pirenzepine, produced dose-dependent antagonism of the enhanced theta wave frequency and hypertensive response produced by arecoline. The differences in antagonist potency for the two responses was less than 6-fold, which indicated that both the increase in hippocampal theta wave activity and increase in blood pressure may have been mediated through muscarinic receptors of the M1 subtype. Further studies using a wider range of antagonists will be required to confirm this conclusion.