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 in the rat prefrontal cortex. Exposure of rats to an environment associated 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 stress. On the other hand, ipsapirone (10 mg/kg, but not 2.5 mg/kg) and buspirone (2.5 mg/kg) enhanced basal outflow of dopamine. When ipsapirone (10 mg/kg) and buspirone (2.5 mg/kg) were given to rats exposed to conditioned stress, the stress-evoked elevation in dopamine outflow was abolished. Ipsapirone in a dose of 2.5 mg/kg was ineffective in the stress 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 operate via serotonergic 5-HT1A receptors. Although ipsapirone and buspirone 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 stress-induced alterations in dopamine outflow are discussed in terms of their possible effectiveness in various types of general anxiety disorders.
Wedzony
K
K
Institute of Pharmacology, Polish Academy of Sciences, Krakøw, Poland.
Maćkowiak
M
M
Fijał
K
K
Gołembiowska
K
K
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013315:Stress, Psychological / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C043077:ipsapirone; D003975:Diazepam; D002065:Buspirone; D004298:Dopamine