Adrenaline in the CNS: In vivo evidence for a functional pathway innervating the hypothalamus

Abstract

This article reviews the evidence, obtained from studies employing the technique of intracerebral dialysis, to monitor changes in extracellular adrenaline in the hypothalamus, that adrenaline is released from nerve endings in the hypothalamus and has a functional role. Studies using [ 3H] adrenaline to determine the specificity of uptake mechanisms for adrenaline indicate that labelled adrenaline is also taken up by noradrenergic nerve endings. This supports the need to develop techniques to monitor changes in endogenous release of adrenaline. In this study, it has been shown that inhibition of phenylethanolamine- N-methyltransferase selectively decreases tissue levels in the hypothalamus and in vivo release of adrenaline, while monoamine oxidase inhibition and antagonism of α 2-adrenoceptors increases the release of both adrenaline and noradrenaline. The “selective” noradrenergic neurotoxin DSP 4 caused an initial increase in the release of both catecholamines, followed by a marked decrease in their release. Stimulation of the adrenaline-containing neurones in the rostral ventrolateral medulla (C 1 region) increased the release of adrenaline in the posterior hypothalamus, but not that of noradrenaline, while also increasing mean arterial blood pressure. Pharmacological evidence indicates that B 2-adrenoceptors in the hypothalamus and the spinal cord are involved in the rise in mean arterial pressure, as the response is reduced by a selective B 2-antagonist (ICI 118551). The rise in mean arterial blood pressure during C 1 stimulation is enhanced by the α 2-antagonist idazoxan, supporting observations that α 2-adrenoceptors are involved in the pre-synaptic regulation of release of adrenaline. The results support a neurotransmitter role for adrenaline in the CNS and demonstrate that this catecholamine, together with other unidentified neurotransmitters, has a function in the central regulation of mean arterial pressure.