Electrophysiological characterization of adrenoceptors in the rat dorsal hippocampus. II. Receptors mediating the effect of synaptically released norepinephrine.

The present studies were undertaken to determine the nature of the receptors mediating the effects of endogenous norepinephrine (NE) released by stimulation of the locus coeruleus (LC) on the firing activity of dorsal hippocampus pyramidal neurons in the rat. Unitary activity of CA3 pyramidal neurons was recorded extracellularly. In most neurons, the LC stimulation produced a period of suppression, followed by a period of activation. The suppression was selectively blocked by prazosin, an alpha 1-adrenoceptor antagonist, whereas the activation was selectively blocked by propranolol, a beta-adrenoceptor antagonist. Idazoxan, an alpha 2-adrenoceptor antagonist, increased the period of suppression without affecting the period of activation. The effectiveness of microiontophoretic applications of NE on the same neurons was reduced by idazoxan, but was modified neither by propranolol nor prazosin. Lesion of the central noradrenergic system by intracerebroventricular 6-hydroxydopamine markedly decreased the NE content in the hippocampus in all rats but the effectiveness of the LC stimulation was reduced only in rats with a depletion greater than 90%. These results demonstrate that the suppressant effect of endogenous NE released by LC stimulation on hippocampus pyramidal neurons is mediated by an alpha 1-adrenoceptor and suggest that its late excitatory effect might involve beta-adrenoceptors. Since the effect of microiontophoretically applied NE on the same neurons is mediated by alpha 2-adrenoceptors, these data provide evidence that, in the rat hippocampus, postsynaptic alpha 1-adrenoceptors are intrasynaptic, whereas postsynaptic alpha 2-adrenoceptors are extrasynaptic.