GABAergic neurosteroid modulation of ethanol actions.
Systemic administration of ethanol elevates plasma and cerebral cortical GABAergic neuroactive steroids. The increase in neurosteroids is responsible for specific behavioural and electrophysiological actions of ethanol in rodents. This article recapitulates the current knowledge of the novel interaction between ethanol and neurosteroids and addresses the potential mechanism for ethanol-induced increase in brain neurosteroid levels. Ethanol-induced increase in the cortical neurosteroid content is modified by neurosteroid biosynthesis inhibitors and completely prevented by adrenalectomy in male rats. In line with this, adrenalectomy prevented the anticonvulsant and hypnotic effects of acute ethanol administration. It is speculated that acute ethanol administration might resemble acute stress and increase neuroactive steroids due to activation of hypothalamic-pituitary adrenal axis. Ethanol-induced increases in neuroactive steroids might be responsible for the antidepressant, anxiolytic, spatial learning deficits and drug discriminatory actions in rodents. Thus ethanol-induced increases in neuroactive steroids represent a novel mechanism of ethanol's action, responsible for several pharmacological and behavioural actions of ethanol. The development of new therapeutic strategies for alcoholism may arise based on the novel interaction between ethanol and neurosteroids in the brain.
Khisti
Rahul T
RT
Departments of Psychiatry and Pharmacology, Bowles Center for Alcohol Studies, CB#7178, 3027 Thurston Bowles Bldg., University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7178, USA.
Penland
Shannon N
SN
VanDoren
Margaret J
MJ
Grobin
A Chistina
AC
Morrow
A Leslie
AL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D018120:Finasteride / Q000009:adverse effects; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D011280:Pregnanolone / Q000378:metabolism; D051381:Rats; D018079:Receptors, GABA / Q000187:drug effects* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D012893:Sleep Wake Disorders / Q000139:chemically induced; D009435:Synaptic Transmission / Q000187:drug effects
D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018120:Finasteride; D011280:Pregnanolone