GAMMA-AMINOBUTYRIC ACID-ACTIVATED CHLORIDE CHANNELS IN RATS SELECTIVELY BRED FOR DIFFERENTIAL ACUTE SENSITIVITY TO ALCOHOL

Effects of various sedative hypnotic agents on GABA-mediated chloride flux were evaluated in whole brain membrane vesicles (microsacs) prepared from rats selectively bred for high (HAS) and low sensitivity (LAS) to an acute hypnotic dose of alcohol. The HAS rats were more sensitive to the effects of pentobarbital, phenobarbital, flunitrazepam, and ethanol on GABA-mediated chloride flux compared with the LAS rats. No differences between the lines in GABA-stimulated chloride flux were observed. Modulation of 1-[H-3]-phenyl-4-butyl-2,6,7-trioxabicyclo(2.2.2)octane([H-3]-TBOB) and [H-3]-diazepam binding also was measured. The lines did not differ in inhibition of [H-3]-TBOB binding by pentobarbital, phenobarbital, muscimol or picrotoxin. Although the lines displayed almost identical K(D) and B(max) for [H-3]-diazepam binding, the GABA agonist, muscimol, was a more potent stimulator of [H-3]-diazepam binding in membranes prepared from HAS rats than from LAS rats. These findings are discussed in light of previous work using other selected lines.