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The effects of glutamate, NMDA and quisqualate on carbachol- and norepinephrine-elicited formation of inositol phosphate (IP) were evaluated in slices prepared from the cerebral cortex of 3- and 24-month Sprague-Dawley rats. Glutamate, NMDA, and quisqualate antagonized the IP response to carbachol in a concentration-dependent fashion. This antagonism was more pronounced in aged than in young rats, both for glutamate (IC5O 0.114 and 0.210 mM) and NMDA (IC5O 0.0029 and 0.127 mM), but not for quisqualate. Glutamate (but not NMDA) also antagonized in a concentration-dependent fashion the IP response to norepinephrine, IC50s were 0.061 and 0.126 mM for aged and young rats, respectively; quisqualate had an inhibitory effect only at 1 mM concentration in the two age-groups, while in aged rats some stimulatory effect was present at 0.1 mM concentration. Glutamate, NMDA and quisqualate (1 mM) did not affect basal IP accumulation in either young or aged rats; quisqualate, however, at 0.1 mM concentration had some stimulatory effect, more pronounced in aged rats. This effect was probably responsible for the biphasic effect of quisqualate in this age-group. The most important finding consists of the demonstration of an age-related increase in the inhibitory effects of NMDA on carbachol-induced IP accumulation. This implies an altered modulation of cholinergic post-receptor mechanisms by glutamatergic mechanisms.

The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated cAMP and inositol phosphate accumulation in rat brain cerebral cortical slices. Under the conditions of these experiments, isoproterenol-induced cAMP accumulation was unaltered by electroschock, although there was a significant reduction in the norepinephrine- and isoproterenol + 6-fluoronorepinephrine-stimulated responses. No change in α-adrenoceptor-mediated inositol phosphate accumulation was noted. The results indicate that electroshock selectively modifies an α-adrenoceptor system in brain that differs from that associated with inositol phosphate accumulation.