MUSCARINIC RECEPTOR SUBTYPE INVOLVEMENT IN BRAIN CHOLINERGIC STIMULATION BY INTRACEREBROVENTRICULAR NEOSTIGMINE IN SINOAORTIC DENERVATED RATS

1. The present studies evaluated the participation of central muscarin ic receptors in the cardiovascular effects of centrally injected neost igmine, a quaternary anticholinesterase, in conscious, sham operated r ats and in sinoaortic denervated animals. 2. The dose dependent presse r effect of neostigmine (0.1 to 1 mu g ICV) was greater in sinoaortic denervated rats than in sham operated animals, but only a dose-depende nt bradycardic effect was seen in sham operated rats. 3. Doses of 3.3 nmol (ICV) of both the Mi muscarinic antagonist, pirenzepine, and the M-3 muscarinic antagonist, 4-DAMP, prevented the presser response to 1 mu g of neostigmine in sham-operated rats and in sinoaortic denervate d animals; however, the MZ muscarinic antagonist, AF-DX116, partially blocked this response in sham-operated rats while failing to do so in sinoaortic denervated rats. In sham rats, doses of 3.3 nmol (ICV) of b oth pirenzepine and 4 DAMP prevented the bradycardic response to 1 mu g (ICV) of neostigmine, whereas AF-DX116 induced a partial blockade. 4 . 4-DAMP, at the dose of 0.3 nmol (ICV), but not pirenzepine at the sa me dose, prevented the presser effect of neostigmine (0.1 co 1 mu g IC V) in both groups of rats. Both muscarinic antagonists at this dose pr evented the bradycardia elicited by the anticholinesterase (0.1 to 1 l ag ICV), but 4-DAMP showed a greater antagonistic action on this cardi ac effect than pirenzepine. In sham operated rats, ICV injection of 0. 3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0. 3 mu g of neostigmine. 5. Results suggest mainly an involvement of bra in M-3-subtype muscarinic receptors in the cardio vascular effect of i ntracerebroventricular administration of anticholinesterase neostigmin e in both groups of rats. (C) 1998 Elsevier Science Inc.