Central effects of muscarinic agonists and antagonists on hippocampal theta rhythm and blood pressure in the anaesthetised rat.
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.
Barnes
J C
JC
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Hertfordshire, U.K.
Roberts
F F
FF
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D012601:Scopolamine / Q000494:pharmacology; D013826:Theta Rhythm / Q000187:drug effects*
D010276:Parasympatholytics; D010277:Parasympathomimetics; D010890:Pirenzepine; D012601:Scopolamine