The anxiolytic beta-carboline ZK 93423 prevents the stress-induced increase in dopamine turnover in the prefrontal cortex.
The effects of electric foot-shock on the activity of the mesocortical dopaminergic (DAergic) neurons were estimated by measuring the changes in dihydrophenylacetic acid (DOPAC) and DA content in the prefrontal cortex of the rat. A marked rise in DOPAC content (+80%) and a significant decrease in DA levels (-23%) were observed after a 20 min foot-shock session. These effects were completely prevented by pretreatment with diazepam (5 mg/kg i.p.). ZK 93423, a recently synthesized beta-carboline with benzodiazepine-like properties, prevented the decrease in DA content induced by foot-shock at the dose of 20 mg/kg. Moreover, the stress-induced increase in DOPAC levels was partly or completely blocked by pretreatment with 20 or 40 mg/kg of ZK 93423, respectively. These results provide further support for the view that the mesocortical DAergic system can be modulated by drugs that selectively interact with the benzodiazepine recognition site.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002243:Carbolines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004597:Electroshock; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D002243:Carbolines; D015102:3,4-Dihydroxyphenylacetic Acid; C042569:ZK 93423; D004298:Dopamine