PT - JOURNAL ARTICLE AU - B. J. HOFFER AU - G. R. SIGGINS AU - A. P. OLIVER AU - F. E. BLOOM TI - ACTIVATION OF THE PATHWAY FROM LOCUS COERULEUS TO RAT CEREBELLAR PURKINJE NEURONS: PHARMACOLOGICAL EVIDENCE OF NORADRENRTGIC CENTRAL INHIBITION DP - 1973 Mar 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 553--569 VI - 184 IP - 3 4099 - http://jpet.aspetjournals.org/content/184/3/553.short 4100 - http://jpet.aspetjournals.org/content/184/3/553.full SO - J Pharmacol Exp Ther1973 Mar 01; 184 AB - A direct pathway of norepinephrine-containing axons can be demonstrated by fluorescence histochemistry to arise in the pontine nucleus locus coeruleus and project to the Purkinje cells of the rat cerebellar cortex. To determine the mechanisms underlying the physiological effects of activating this pathway, a pharmacological analysis has been performed by microelectrode techniques. Discrete stimulation of the locus coeruleus inhibits the discharge of cerebellar Purkinje cells. This inhition derives from a hypenpolarization of the Purkinje cell membrane accompanied by no increase in membrane ionic conductance, as shown in previous experiments with iontophoretic administration of norepinephrine and cyclic adenosine monophosphate. The magnitude of the hyperpolarizing response is not related to the initial resting membrane potential. Destruction of the central norepinephrine fiber systems by pretreatment with 6-hydroxydopamine or acute depletion of norepinephrine content by reserpine and α-methyltyrosine blocks the effects of stimulating locus coeruleus. Inhibitions of Purkinje cells produced by stimulation of locus coeruleus are also blocked by iontophoretic administration of prostaglandins E1 and E2 and potentiated by iontophoretic administration of papaverine. Purkinje cell inhibitions produced by activaton of non-noradrenergic Pathways are not similarly affected by any of these treatments. These data provide evidence that activation of the locus coeruleus inhibits the Purkinje cells by a norepinephrine-mediated mechanism. © 1973 by The Williams & Wilkins Co.