Age-related differences in neurosteroid potentiation of muscimol-stimulated (36)C1(-) flux following chronic ethanol treatment

Alcoholism and alcohol abuse create costly social and economic problems in many nations. Recent studies indicate that alcohol exposure during adolesce nce may convey unique risks for subsequent neurocognitive deficits and prob lem drinking. Although GABAA receptor function is one of the principle neur ochemical targets of ethanol action in the adult brain, little is known abo ut the effects of alcohol on this system during adolescence. Adolescent (30-day-old) and adult (90-day-old) male rats were intermittentl y exposed to ethanol for 1 month. At various times after the end of the exp osure period, synaptoneurosomes were prepared from their cerebral cortices. GABAA receptor-mediated Cl-36(-) influx was measured in the absence and pr esence of the neurosteroid 3 alpha ,21-dihydroxy-5 alpha -pregnan-20-one (T HDOC). In tissue from ethanol-exposed animals, sensitization to the potenti ating effects of the neurosteroid was apparent 5 and 12 days after ethanol withdrawal. This sensitization was more apparent at the low concentrations of THDOC in animals pretreated with ethanol as adolescents. Sensitization to the potentiating effects of a neurosteroid is an enduring phenomenon, persistent long after the acute phase of ethanol withdrawal, an d may be indicative of long-term changes in GABAA receptor function. Enhanc ed neurosteroid sensitization in animals pretreated as adolescents is consi stent with the notion that adolescence is a period of unique sensitivity to the effects of ethanol. This uniqueness may now be extended to the chronic effects of ethanol. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.