Electrophysiological characterization of adrenoceptors in the rat dorsal hippocampus. III. Evidence for the physiological role of terminal alpha 2-adrenergic autoreceptors.

The present electrophysiological studies were undertaken to assess the role of terminal alpha 2-adrenergic autoreceptors in regulating noradrenergic synaptic transmission in the rat CNS. The effectiveness of the electrical stimulation of the locus coeruleus (LC) in suppressing the firing activity of pyramidal neurons was determined in the dorsal hippocampus. Intravenous clonidine, an alpha 2-adrenergic agonist, decreased the effectiveness of the LC stimulation, without altering the effect of microiontophoretically applied norepinephrine. The subsequent i.v. administration of low doses of idazoxan, an alpha 2-adrenergic antagonist, reversed this effect of clonidine on the LC stimulation. To ascertain that the effect of clonidine administered i.v. was indeed attributable to its action on noradrenergic terminals, it was applied locally by microiontophoresis; it decreased the effectiveness of the LC stimulation. Another paradigm used to assess the function of terminal alpha 2-adrenoceptors was to increase the frequency of the LC stimulation from 1 to 5 Hz. This resulted in a 5-fold decrease of the effectiveness of the stimulation. That this was attributable to an enhanced activation of terminal alpha 2-adrenoceptors was suggested by the reversal of this effect of increasing the frequency of the LC stimulation by intravenous idazoxan. Furthermore, the degree of enhancement of the effectiveness of the LC stimulation by idazoxan was much greater at 5 than at 1 Hz. These results provide novel electrophysiological evidence for the potent regulatory role of terminal alpha 2-adrenoceptors on noradrenergic neurotransmission.