Stress and beta-carbolines decrease the density of low affinity GABA binding sites; an effect reversed by diazepam.
Cerebral cortex membranes from rats habituated to manipulations preceding decapitation (habituated rats) had 40% higher GABA binding than membranes from naive animals. Diazepam (5 X 10(-6) M), added to membranes from naive rats, increased GABA binding to the level of habituated rats, but failed to induce any further increase in membranes from the latter animals. Vice versa, beta-carbolines (FG 7142, beta-CCE, DMCM) added to membranes from habituated rats lowered GABA binding to the level of naive animals, but caused no further decrease in the membranes from this last group. Diazepam removed the effect of beta-carbolines in membranes from habituated rats. It is suggested that handling represents a stressful stimulus for naive animals and that stress lowers GABA binding by releasing an endogenous ligand for benzodiazepine receptors possessing similar properties to beta-carbolines. Finally, the results indicate that the emotional status of animals from which brain tissue is obtained should be considered when connections between GABA and benzodiazepine receptors are studied.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology*; D006234:Handling, Psychological; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013312:Stress, Physiological / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002243:Carbolines; D007211:Indoles; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D005680:gamma-Aminobutyric Acid; C035874:FG 7142; C024915:beta-carboline-3-carboxylic acid ethyl ester; D003975:Diazepam