Brain Stem Catecholamines Circuitry: Activation by Alcohol and Role in the Hypothalamic-Pituitary-Adrenal Response to this Drug

Abstract

Although the stimulatory effect of alcohol on the rat hypothalamic-pituitary-adrenal (HPA) axis is well known, the mechanisms underlying this influence remain poorly understood. In the present study, we tested the hypothesis that brain catecholamines play an important role in this response. As expected, the acute intragastric administration of alcohol to adult male rats elevated plasma adrenocorticotrophic hormone (ACTH) levels and activated hypothalamic corticotrophin-releasing factor neurones. Novel findings pertain to the effect of alcohol on, and the role played by, brain adrenergic circuits. We first observed that alcohol up-regulated c-fos signals in the locus coeruleus, the main noradrenergic brain cell group; and that it activated (nor)adrenergic medullary cells (A1-A2/C1-C3). Evidence for the role played by these catecholaminergic circuits then came from the observation that blockade of α(1) -, but not β-, adrenergic receptors interfered with alcohol-induced ACTH secretion; and that depletion of catecholaminergic input to the paraventricular nucleus (PVN) by the toxin 6-hydroxydopamine significantly decreased the ACTH response to alcohol. Finally, destruction of the A1-A2/C1-C3 region with the immunotoxin anti-dopamine-B-hydroxylase-saporin interfered with the catecholaminergic input to the PVN. Collectively, our work extends our knowledge of the ability of this drug to up-regulate catecholamine circuitry in the rat brain. It also shows that medullary catecholamine innervation of the hypothalamus plays an important role in modulating the stimulatory effect of alcohol on the HPA axis, an effect exerted through activation of α(1) -adrenergic receptors.