Extranuclear dendrites of locus coeruleus neurons: activation by glutamate and modulation of activity by alpha adrenoceptors.

1. Locus coeruleus (LC) neurons were recorded extracellularly and intracellularly in rat brain slices. Effects of glutamate applied to the area of distal extranuclear LC dendrites, and of alpha-2 adrenoceptors applied in the bath, were determined on activity of these cells. 2. Glutamate applied to the area of distal dendrites potently activated LC neurons. These responses were not blocked by either 1 microM tetrodotoxin or 2 mM Co(2+)-10 mM Mg2+. This indicates that glutamate acting directly on distal dendrites can potently activate LC neurons. 3. Bath application of the alpha-2 adrenoceptor antagonists yohimbine (1 microM) or idazoxan (1 microM) significantly increased responses of LC neurons evoked by dendritic glutamate application. These antagonist treatments also transiently decreased, and then increased, spontaneous discharge activity in LC neurons. 4. Alterations in spontaneous and glutamate-evoked activities after blockade of alpha-2 adrenoreceptors were not observed in LC neurons of reserpinized rats. This indicates that the altered LC activity and responsiveness to glutamate following alpha-2 antagonist treatment in nonreserpinized slices are mediated via blockade of effects of endogenously released noradrenaline. 5. The alpha-1 antagonist prazosin (1 microM) caused a small but reliable decrease in the spontaneous firing rate of LC neurons. After prazosin pretreatment, alpha-2 antagonists did not evoke the expected delayed increase in LC spontaneous firing and response to glutamate application. These results indicate that activation of alpha-1 adrenoceptors may contribute to the delayed increase in excitability of LC neurons after alpha-2 antagonist administration. The possible roles of alpha-1 and alpha-2 adrenoreceptors in regulation of spontaneous discharge rate and glutamate-evoked responses in LC neurons are discussed.