The anxiogenic beta-carboline FG 7142 selectively increases dopamine release in rat prefrontal cortex as measured by microdialysis.
The effect of the anxiogenic beta-carboline methyl-beta-carboline-3-carboxyamide (FG 7142) on dopamine release in prefrontal cortex and striatum in the awake freely moving rat was determined using the technique of microdialysis. FG 7142 (25 mg/kg, i.p.) caused a time-dependent increase in dopamine release in prefrontal cortex which was statistically significantly greater than the response to vehicle administration. Dopamine release in striatum was unaltered by FG 7142. Pretreatment of animals with the benzodiazepine antagonist Ro 15-1788 (30 mg/kg, i.p., 15 min prior to FG 7142 administration) completely abolished the increase in dopamine release caused by FG 7142 in prefrontal cortex. These data indicate that the anxiogenic benzodiazepine inverse agonist FG 7142 can selectively increase dopamine release in prefrontal cortex, and that this effect appears to be mediated via the gamma-aminobutyric acid/benzodiazepine receptor complex.
Bradberry
C W
CW
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Lory
J D
JD
Roth
R H
RH
D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D002243:Carbolines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D003956:Dialysis / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D005442:Flumazenil / Q000494:pharmacology; D005625:Frontal Lobe / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002243:Carbolines; D001569:Benzodiazepines; D005442:Flumazenil; C035874:FG 7142; D004298:Dopamine