ADRENALECTOMY AND STRESS MODULATE GABA-A RECEPTOR FUNCTION IN LS AND SS MICE

The effects of manipulation of adrenal steroids by adrenalectomy (ADX) or stress on GABA(A) receptor function were characterized in long-sleep (LS) and short-sleep (SS) mice. 36Chloride flux was not altered in either line of mouse after ADX; however, exposure to a behavioral stressor resulted in a highly significant inhibition of ion channel activity measured in cortical membranes from both LS and SS mice. Adrenalectomy also had no effect on [H-3]FNZ binding; whereas exposure to stress differentially altered benzodiazepine binding in LS and SS mice. In LS cortex both B(max) and K(d) values increased, whereas in SS cerebellum, B(max) and K(d) values were decreased after stress. In SS mice ADX did not affect GABA-enhancement of [H-3]FNZ binding. In LS mice, however, ADX resulted in a potentiation of GABA-enhanced [H-3]FNZ binding in cortex and an inhibition of enhancement in cerebellum. Corticosterone (CCS) replacement in ADX-LS mice returned enhancement values to those of sham-operated mice, indicating a role for basal levels of CCS in maintaining normal receptor coupling function in this line of mouse. These results suggest that GABA(A) receptor sensitivity is more labile under stressful conditions. Differential receptor responses to adrenal manipulation between LS and SS mice may be due to genetic variation in GABA(A) receptor subunit combinations in these lines of mice.