Involvement of GABA-A receptor chloride channel complex in isolation stress-induced free choice ethanol consumption in rats.
The present study revealed the effect of diazepam, a benzodiazepine, and progesterone, a pregnane precursor of neurosteroids, which act via modulating GABA-A chloride channel complex on the isolation stress-induced free choice ethanol consumption in adult rats. Isolation stress for 24 hr over a period of 6 days produced a significant increase in ethanol consumption, which persisted during the 6-day recovery period. Pretreating the animals with diazepam (5 mg/kg, i.p.), or progesterone (5 mg/kg, i.p.), blocked the isolation stress-induced increase in ethanol consumption. Bicuculline (2 mg/kg, i.p.), a GABA-A receptor antagonist significantly attenuated the effect of both diazepam and progesterone on stress-induced modulation of ethanol consumption. Isolation stress also caused an increase in total fluid consumption, which was antagonised by both diazepam and progesterone. Like ethanol consumption, this effect of diazepam and progesterone on isolation stress-induced increase in total fluid consumption was attenuated by bicuculline. Neither diazepam nor progesterone produced an increase in ethanol consumption in non-stressed rats. However, unlike diazepam, progesterone administration to non-stressed rats caused a significant increase in total fluid consumption. Results of the present study thus show that GABAergic mechanisms may be playing an important role in isolation stress-induced increase in ethanol consumption.
Mediratta
Pramod K
PK
Department of Pharmacology, University College of Medical Sciences and GTB Hospital, Delhi 110 095, India. drpramod_k@yahoo.com
Mahajan
Prabha
P
Sharma
Krishna K
KK
Bhandari
Rishabh
R
Dubey
Shitla P
SP
D000818:Animals; D018118:Chloride Channels / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*
D018118:Chloride Channels; D011963:Receptors, GABA-A; D000431:Ethanol; D011374:Progesterone; D003975:Diazepam