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

Journal Article (Journal Article)

Alcoholism and alcohol abuse create costly social and economic problems in many nations. Recent studies indicate that alcohol exposure during adolescence may convey unique risks for subsequent neurocognitive deficits and problem drinking. Although GABA(A) receptor function is one of the principle neurochemical targets of ethanol action in the adult brain, little is known about the effects of alcohol on this system during adolescence. Adolescent (30-day-old) and adult (90-day-old) male rats were intermittently exposed to ethanol for 1 month. At various times after the end of the exposure period, synaptoneurosomes were prepared from their cerebral cortices. GABA(A) receptor-mediated 36Cl(-) influx was measured in the absence and presence of the neurosteroid 3alpha,21-dihydroxy-5alpha-pregnan-20-one (THDOC). In tissue from ethanol-exposed animals, sensitization to the potentiating 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, and may be indicative of long-term changes in GABA(A) receptor function. Enhanced neurosteroid sensitization in animals pretreated as adolescents is consistent 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.

Full Text

Duke Authors

Cited Authors

  • Grobin, AC; Matthews, DB; Montoya, D; Wilson, WA; Morrow, AL; Swartzwelder, HS

Published Date

  • 2001

Published In

Volume / Issue

  • 105 / 3

Start / End Page

  • 547 - 552

PubMed ID

  • 11516822

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/s0306-4522(01)00232-9


  • eng

Conference Location

  • United States