Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy.
Rats exposed to inescapable tailshock exhibit deficits in learning a simple shuttlebox escape task 24 h later. This syndrome has been termed 'behavioral depression' or 'learned helplessness', and is a model of stress-induced depression. In the present study a significant (25%) decrease in GABA receptor-mediated chloride ion flux as measured by muscimol-stimulated 36Cl- uptake in synaptoneurosomes was found in the cerebral cortices of rats that failed the shuttlebox task as compared to naive control rats. Rats which were exposed to tailshock and subsequently learned the escape task did not show a significant difference in muscimol-stimulated 36Cl- uptake as compared to naive control rats. Similarly, rats that failed to learn the shuttlebox escape task had significantly lower in vivo [3H]Ro15-1788 specific binding in cerebral cortex (43%), hippocampus (35%) and striatum (33%) as compared to naive control rats. In cerebellum and hypothalamus, there were significant reductions in specific [3H]Ro15-1788 binding in both animals that failed and animals that learned the shuttlebox escape task as compared to naive controls. To control the stress of the footshock associated with the shuttlebox escape task, we investigated the effect of gridshock in which total footshock received was equivalent to that received by rats who failed the shuttlebox task. There were no differences in muscimol-stimulated 36Cl- uptake or in vivo [3H]Ro15-1788 specific binding between naive controls and rats administered footshock independent of a learning task. These data suggest that the development of stress-induced behavioral depression may be associated with a decrease in GABA receptor-mediated chloride channel function.
Drugan
R C
RC
Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892.
Morrow
A L
AL
Weizman
R
R
Weizman
A
A
Deutsch
S I
SI
Crawley
J N
JN
Paul
S M
SM
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002712:Chlorides / Q000493:pharmacokinetics*; D003863:Depression / Q000209:etiology* / Q000378:metabolism; D005442:Flumazenil / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013312:Stress, Physiological / Q000150:complications* / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism / Q000502:physiology
D002712:Chlorides; D011963:Receptors, GABA-A; D009118:Muscimol; D005442:Flumazenil