Roles of the Locus Coeruleus and Adrenergic Receptors in Brain-Mediated Hypothalamic-Pituitary-Adrenal Axis Responses to Intracerebroventricular Alcohol

摘要

ALCOHOL HAS LONG been known to disrupt normal hypothalamic-pituitary-adrenal (HPA) axis function. In addition, the effects of the drug on HPA activity have been linked to both the genesis and maintenance of addiction, although the mechanisms underlying this are uncertain (Lovallo, 2006). Alcohol and its metabolites stimulate the HPA axis by their direct actions on its tissues and indirectly by altering peripheral physiological parameters that feedback to the hypothalamus and activate the axis. For instance, at the level of the brain, alcohol administered by intracerebroventricular (icv) injection causes an increase in the release of corticotropin-releasing factor (CRF), the main hypothalamic hormone that drives the release of the pituitary stress hormone adrenocorticotropin (ACTH) (Lee et al, 2004). In the periphery, acetaldehyde, the drug's main metabolite, stimulates corticosterone secretion at the level of the adrenal glands (Cobb and Van Thiel, 1982). Alcohol can also cause gastrointestinal irritation, induce liver cytokine production, and produce changes in blood pressure and body temperature (El-Mas et al., 2006; Linnoila et al., 1979; Narkiewicz et al., 2000; Schaffert et al., 2009), all of which constitute homeostatic challenges that are perceived at the Wei nf the brain and indirectly stimulate HPA activity.