The action of stress and anxiolytic and anxiogenic benzodiazepine receptors ligands on [35S] T-butylbicyclophosphorothionate binding in the rat cerebral cortex.
The effect of foot shock stress on [35S] t-butylbicyclophosphorothionate (TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of positive and negative modulators of the GABAergic transmission. 35S-TBPS binding was increased (30%) in cerebral cortex of rats exposed to foot shock compared to the non stressed rats. In contrast, the in vitro addition and the in vivo administration of anxiolytic and positive modulators of the GABAergic transmission inhibited the specific binding of 35S-TBPS. On the other hand, the anxiogenic beta-carbolines DMCM, beta CCM, FG 7142 and beta CCE mimicked in vivo and in vitro the effect of stress. The demonstration that stress, similar to anxiogenic beta-carbolines and opposite to benzodiazepines and anxiolytic beta-carbolines, increases 35S-TBPS binding in the rat cerebral cortex, suggests that some emotional state related to stress and anxiety may result from a diminished GABAergic transmission at the level of the GABA/benzodiazepine receptor/chloride ionophore complex.
Dipartimento di Biologia Sperimentale, Università degli Studi, Cagliari, Italy.
A
A
Concas
M
M
Serra
E
E
Sanna
G
G
Biggio
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004347:Drug Interactions; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D002243:Carbolines; D002712:Chlorides; D007473:Ion Channels; D011963:Receptors, GABA-A; C037476:tert-butylbicyclophosphorothionate