Alpha-2 receptor blockade increases responsiveness of locus coeruleus neurons to excitatory stimulation

This study presents evidence that alpha 2-receptors in the locus coeruleus (LC) regulate the responsiveness of LC neurons to excitatory stimuli. In the first experiment, intravenous administration of the alpha 2-adrenergic antagonist idazoxan markedly potentiated the responses of LC neurons to the excitatory stimulus of contralateral hind paw compression (PC). Increased responsiveness of LC neurons to PC was seen with doses of idazoxan far below those that altered spontaneous activity of the LC. In the second experiment, increased responsiveness of LC neurons to PC was seen when low doses of idazoxan were infused directly into the LC, thereby indicating that increased responsiveness of LC neurons resulted from blockade of alpha 2-receptors in the LC region and not from greater stimulus input to the LC resulting from blockade of alpha 2-receptors elsewhere. In the third experiment, another alpha 2-adrenergic antagonist, yohimbine, also increased the responsiveness of LC neurons to PC. Finally, the response of the LC to another excitatory stimulus, peripheral injection of nicotine, was also found to be increased by idazoxan. Results obtained prior to these studies had indicated that alpha 2-receptors in the LC regulate the period of quiescence that follows a burst of LC firing. However, more recent studies suggest that this quiescence results primarily from changes in ionic conductance of the membrane following directly from depolarization. The present findings indicate that, in addition to whatever role alpha 2-receptors play in regulating postfiring quiescence, these receptors in the LC appear to play a major role in regulating the responsiveness of LC neurons to excitational influences.