Although it is well documented that stress can increase the activity of central dopamine and norepinephrine neurons, little is known about the role of other neurotransmitters in modulating this response. Previous studies have implicated corticotropin-releasing hormone in modulating stress-evoked changes in the activity of locus coeruleus neurons. The present study examines whether corticotropin-releasing hormone contributes to stress-evoked increases in extracellular norepinephrine and dopamine in rat medial prefrontal cortex, as monitored by in vivo microdialysis. As noted previously, 30 min of tail-shock increased extracellular levels of norepinephrine and dopamine in the medial prefrontal cortex of naïve rats, and this was enhanced in rats previously exposed to chronic cold ( approximately 5 degrees C for 2-3 weeks). Previous intraventricular administration of a corticotropin-releasing hormone antagonist (D-Phe-corticotropin-releasing hormone; 3 and 9 microg) did not alter the tail-shock evoked in increase in extracellular levels of norepinephrine and dopamine in either naïve or chronically cold-exposed rats. Intraventricular administration of 3 microg of D-Phe-corticotropin-releasing hormone attenuated the increase in extracellular norepinephrine induced by co-administration of 3 microg of corticotropin-releasing hormone, confirming the efficacy of this compound. Results of the present study suggest that endogenous corticotropin-releasing hormone does not play a role in modulating the release of norepinephrine and dopamine occurring in response to acute tail-shock or the expression of a potentiated response to tail-shock in rats exposed chronically to cold.