Stress-induced increase in brain neuroactive steroids: antagonism by abecarnil.
Acute foot shock stress elicits a selective and time-dependent increase of neuroactive steroid (pregnenolone, progesterone, allotetrahydrodeoxycorticosterone) concentrations in rat brain cortex, accompanied by a marked increase of plasma corticosterone. The brain cortical neuroactive steroid levels peaked between 10 and 30 min poststress and returned to control values by 2 h. Abecarnil (0.3 mg/kg), i.p.), a beta-carboline derivative with anxiolytic properties, completely antagonized the effect of foot shock on brain cortical neuroactive steroids. A single administration of the anxiogenic beta-carboline FG 7142 (15 mg/kg, i.p.), in contrast, mimicked the effect of foot shock. These data support the hypothesis for the existence of a functional relationship between brain neuroactive steroid concentrations and GABAA receptor function/emotional state of the animal.
Barbaccia
M L
ML
Department of Experimental Medicine, University of Rome Tor Vergata, Italy.
Roscetti
G
G
Bolacchi
F
F
Concas
A
A
Mostallino
M C
MC
Purdy
R H
RH
Biggio
G
G
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002243:Carbolines / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000633:toxicity; D004597:Electroshock; D058787:GABA-A Receptor Antagonists; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D013256:Steroids / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D014151:Anti-Anxiety Agents; D002243:Carbolines; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D013256:Steroids; D002245:Carbon Dioxide; D005680:gamma-Aminobutyric Acid; C062769:abecarnil