Interaction of ethanol and stress with the GABA/BZ receptor in LS and SS mice.
The interaction of stress and ethanol with the GABA/BZ receptor system was evaluated in LS and SS mice. The effects of two separate in vivo treatments, a 2.5 g/kg injection of ethanol or a behavioral stressor, on GABA-enhanced [3H]-FNZ binding were nearly identical in both lines of mice. A 2.5 g/kg ethanol- or stress-pretreatment resulted in increased enhancement in SS cortex, but not LS. In cerebellum, treatment effects were demonstrated in both SS and LS mice. Intraperitoneal injections of increasing doses of ethanol produced biphasic stimulation of GABA-enhanced [3H]-FNZ binding in LS brain regions, but not SS. Adrenalectomies performed one week prior to ethanol administration produced a loss of ethanol enhancement in cerebellum of both lines. However, in cortex, removal of the adrenals had no effect. The in vitro addition of 30 mM ethanol to brain preparations incubated at 37 degrees C from stressed and unstressed animals resulted in greater enhancement of binding in cortex, but not cerebellum of stressed mice. Differences in the degree of enhancement between the lines of mice were lost if the animals were stressed prior to sacrifice or if membrane preparations were incubated at 4 degrees C. The results of this study suggest that the interaction between ethanol and stress is mediated by the GABAergic system, but responses vary dependent on brain region, dose of ethanol, and degree of ethanol sensitivity.
Bowers
B J
BJ
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Wehner
J M
JM
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012890:Sleep / Q000502:physiology; D013312:Stress, Physiological / Q000378:metabolism*
D011963:Receptors, GABA-A; D000431:Ethanol; D005445:Flunitrazepam