Activation of Lateral Geniculate Neurons by Locus Coeruleus or Dorsal Noradrenergic Bundle Stimulation: Selective Blockade by the Alpha 1-adrenoceptor Antagonist Prazosin

Presentation of a stimulus train to the locus coeruleus (LC) or dorsal noradrenergic bundle (DB) resulted in a facilitation of the spontaneous firing of single units in the dorsal lateral geniculate nucleus (LGNd) of the rat. These stimulation effects were blocked by the alpha 1-adrenoceptor antagonists WB-4101 and prazosin. Both drugs also blocked the activation of LGNd neurons by iontophoretic norepinephrine (NE). The cholinergic agonists acetylcholine (ACh) and carbachol (CCh) activated LGNd neurons in a similar fashion to NE, however, these responses were selectively blocked by the muscarinic antagonist scopolamine. The response to ACh was also sensitive to WB-4101 suggesting that the drug possesses some cholinergic blocking activity. In contrast to WB-4101, prazosin displayed a high degree of selectivity for noradrenergic but not cholinergic responses. On the basis of the observation that prazosin selectively antagonizes both the stimulation effects and iontophoretic NE (but not CCh), we conclude that activation of LGNd neurons by LC or DB stimulation is mediated predominantly via the release of NE from coeruleo-geniculate fibers, rather than the inadvertent activation of a cholinergic pathway. Moreover, inasmuch as the systemic administration of prazosin effectively blocks central noradrenergic neurotransmission at doses comparable to those used clinically, the possibility that prazosin exerts its antihypertensive action in part via a central mechanism requires further investigation.