Blockade of α 2-adrenergic receptors, but not blockade of γ-aminobutyric acid a, serotonin, or opiate receptors, augments responsiveness of locus coeruleus neurons to excitatory stimulation

Abstract

Previous studies in this laboratory indicated that alpha 2-adrenergic receptors in the locus coeruleus play a major role in regulating the responsiveness of neurons in the locus coeruleus to excitatory influences. The present study points to the possibility that alpha 2-receptors are unique among inhibitory receptors in the locus coeruleus in regulating responsiveness of these neurons independently of the spontaneous firing rate. In the first part of the study, blockade of alpha 2-receptors was shown to markedly augment responsiveness of neurons in the locus coeruleus to the excitatory stimulus of compression of the contralateral hind paw at doses of an alpha 2-blocker both above and well below those necessary to increase spontaneous activity of neurons in the locus coeruleus. In contrast, blockade of γ-aminobutyric acid and serotonin receptors augmented spontaneous firing rates of neurons in the locus coeruleus but failed to augment responsiveness of these neurons to compression of the hindpaw. Blockade of opiate receptors failed to increase either spontaneous firing rates or the responsiveness of neurons of the locus coeruleus to paw compression; moreover, in animals given an opiate agonist over a number of days to produce tonic stimulation of opiate receptors, blockade of opiate receptors augmented spontaneous firing rates of neurons in the locus coeruleus but had no effect on responsiveness to paw compression. In that blockade of each type of inhibitory receptor tested increased the spontaneous firing rates of neurons in the locus coeruleus but only blockade of alpha 2-receptors increased the responsiveness of neurons in the locus coeruleus to stimulation, without affecting the spontaneous firing rate, alpha 2-receptors may be unique among inhibitory receptors in independently regulating the responsiveness of neurons in the locus coeruleus. One possibility discussed for why alpha 2-receptors regulate the responsiveness, independently of the spontaneous firing rate, is that there are two types of alpha 2 -receptors in the locus coeruleus, one of which regulates responsiveness and another which regulates the spontaneous firing rate.