No abstract

Intoxicating levels of ethanol per se do not result in activation of the hypothalamic-pituitary-adrenal axis in humans. However, gastrointestinal side-effects induced by the ethanol do result in such activation, which appears to be mediated by AVP as the dominant ACTH secretagogue. One of the factors which influences the blood ethanol level at which GI side-effects occur appears to be background alcohol intake.

Antidepressant drugs can exert significant effects on the mood of a patient suffering major depression and other disorders. These drugs generally have pharmacological actions on the uptake or metabolism of the neurotransmitters serotonin, noradrenaline and, to a lesser extent, dopamine. However, there are many aspects of antidepressant action we do not understand. We have applied proteomic analysis in a rat hippocampal model in an attempt to identify relevant molecules that operate in pathways functionally relevant to antidepressant action. Rats were administered either 5 mg/kg daily of the antidepressant paroxetine or vehicle for 12 days, then hippocampal protein was recovered and resolved by 2-D gel electrophoresis. After antidepressant exposure, we observed increased expression or modification of cytochrome c oxidase, subunit Va, cyclin-dependent kinase inhibitor 2A interacting protein, dynein, axonemal, heavy polypeptide 3 and RHO GDP-dissociation inhibitor alpha. Decreased expression or modification was observed for complexin 1 (CPLX1), alpha-synuclein, parvalbumin, ribosomal protein large P2, prohibitin, nerve growth factor, beta subunit (NGFB), peroxiredoxin 6 (PRDX6), 1-acylglycerol-3-phosphate O-acyltransferase 2_predicted, cystatin B (CYTB) and lysosomal membrane glycoprotein 1. CPLX1, the most strongly regulated protein observed, mediates the fusion of cellular transport vesicles with their target membranes and has been implicated in the pathophysiology of mood disorders, as well as antidepressant action. CPLX1 and the other proteins identified may represent links into molecular processes of importance to mood dysregulation and control, and their respective genes may represent novel candidates for studies of antidepressant pharmacogenetics.

C-carriers at rs7566605, possibly regulating the homeostasis gene INSIG2, lost significantly less weight in this lifestyle intervention study. This effect was reversed by carnitine supplementation.