EVIDENCE THAT CONDITIONED STRESS ENHANCES OUTFLOW OF DOPAMINE IN RAT PREFRONTAL CORTEX - A SEARCH FOR THE INFLUENCE OF DIAZEPAM AND 5-HT1A AGONISTS

We evaluated the impact of conditioned stress on outflow of dopamine i n the rat prefrontal cortex. Exposure of rats to an environment associ ated with aversive stimuli-foot shock enhanced outflow of dopamine in a similar way as seen during the conditioning session when foot shocks were applied. Diazepam (2.5 and 10 mg/kg) dose-dependently decreased outflow of dopamine and, when given in a dose of 10 mg/kg, but not 2.5 mg/kg, decreased enhanced dopamine outflow evoked by conditioned stre ss. On the other hand, ipsapirone (10 mg/kg, but not 2.5 mg/kg) and bu spirone (2.5 mg/kg) enhanced basal outflow of dopamine. When ipsapiron e (10 mg/kg) and buspirone (2.5 mg/kg) were given to rats exposed to c onditioned stress, the stress-evoked elevation in dopamine outflow was abolished. Ipsapirone in a dose of 2.5 mg/kg was ineffective in the s tress paradigm tested. It is concluded that conditioned stress in vivo enhances dopaminergic neurotransmission in the rat prefrontal cortex, this effect being attenuated by diazepam, a classic anxiolytic drug, and by such novel anxiolytics as ipsapirone and buspirone, which opera te via serotonergic 5-HT1A receptors. Although ipsapirone and buspiron e blocked stress-induced enhancement of dopamine outflow, this effect seems to result from their influence on the basal outflow of dopamine. Differential effects of diazepam and 5-HT1A agonists on basal and str ess-induced alterations in dopamine outflow are discussed in terms of their possible effectiveness in various types of general anxiety disor ders. (C) 1996 Wiley-Liss, Inc.