Dissociation of locus coeruleus activity and blood pressure: Effects of clonidine and corticotropin-releasing factor

Abstract

In order to determine whether pharmacologically-induced alterations in the spontaneous activity of neurons in the locus coeruleus are associated with changes in blood pressure, the activity of the locus coeruleus and blood pressure were recorded simultaneously in anesthetized rats after the administration of agents known to affect both of these parameters. Spontaneous activity of the locus coeruleus was decreased by intracerebroventricular (i.c.v.) administration of both clonidine and St 91, [2,(2,6-diethylphenylimino)imidazolidine chloride], a charged analogue of clonidine. However, only clonidine decreased the mean blood pressure after intracerebroventricular administration suggesting that either the receptors mediating decreases in the activity of the locus coeruleus are different to those mediating hypotension, or that St 91 does not distribute to sites involved in the control of blood presure even after intracerebroventricular administration. Intravenous administration of clonidine, but not of St 91, decreased the activity of the locus coeruleus and produced a prolonged hypotension, thus suggesting a central mechanism for these effects. Both clonidine and St 91 administered intravenously, produced a brief initial period of hypertension which was not associated with consistent changes in the spontaneous activity of the locus coeruleus. Thus, noradrenergic agonists can decrease the activity of the locus coeruleus without affecting blood pressure, and increase blood pressure without affecting the activity of the locus coeruleus. The spontaneous activity of cells in the locus coeruleus was increased by 100% after the intracerebroventrieular administration of corticotropin-releasing factor (CRF; 3.0 μg). However, blood pressure was not altered by this dose of corticotropin-releasing factor. This demonstrates that increasing the spontaneous activity of the locus coeruleus does not directly affect blood pressure. The results of the present study demonstrate that the activity of the locus coeruleus can be decreased or increased without a resulting change in blood pressure, and conversely, that an increase in blood pressure need not be accompanied by changes in the spontaneous activity of the locus coeruleus.