Cerebral cortical muscarinic cholinergic and N-methyl- d-aspartate receptors mediate increase in cortical blood flow elicited by chemical stimulation of periaqueductal gray matter

Abstract

The periaqueductal gray matter is implicated in the central processing of defensive reactions. We found previously that, when stimulated by N-methyl- d-aspartate, the caudal third of its lateral subdivision elicited an increase in blood flow over widespread cerebral neocortical areas and that a major proportion of the flow increase was inhibited by topical cortical application of scopolamine, an antagonist of muscarinic receptors. The present study was undertaken to elucidate the roles of cortical nicotinic and excitatory amino acid receptors in the mediation of the flow increase in 66 anaesthetized, cervically cordotomized, artificially ventilated rats with open cranial windows. We found that the flow increase (laser–Doppler flowmetry) was resistant to antagonists of non- N-methyl- d-aspartate receptors and of nicotinic receptors. The response was, however, attenuated to a substantial extent by topical and intravenous N-methyl- d-aspartate receptor antagonists, MK-801 and topical d(-)-2-amino-5-phosphonopentanoic acid. Combined topical application of the latter antagonist with scopolamine attenuated the flow increase to a further extent beyond that achieved with either of the antagonists alone. Topical applications of acetylcholine and N-methyl- d-aspartate individually increased the cortical blood flow. A modest synergism was observed between the actions of these two agonists. Overall, we suggest that in the face of stimuli which provoke defensive reactions, the periaqueductal gray matter may elicit an increase in cortical blood flow by utilizing the cortical acetylcholine–muscarinic receptor system and the cortical excitatory amino acid– N-methyl- d-aspartate receptor system. The vasomotor actions of these two transmitter–receptor systems may operate independently of each other as well as in harmony with each other.