Psychological stress increases dopamine turnover selectively in mesoprefrontal dopamine neurons of rats: reversal by diazepam.

The effects of psychological stress on catecholamine and indoleamine metabolism were examined in various brain regions of rats. Psychologically stressed rats were exposed to emotional responses of foot-shocked rats, but were themselves prevented from receiving foot-shock. Psychological stress for 30 min resulted in significant increases of both 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in the medial prefrontal cortex (MPFC), but not in other dopamine (DA) terminal fields. The levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were unaffected in all brain regions examined after 30 min of psychological stress. A small but significant increase of DOPAC levels in the ventral tegmental area (VTA) was observed after a shorter (10 min) duration of stress. Moreover, an increase of DOPAC levels in the MPFC 30 min after psychological stress was attenuated by diazepam (5 mg/kg), and this attenuating effect was antagonized by Ro 15-1788 (15 mg/kg). These results suggest that mesoprefrontal DA neurons are selectively activated by psychological stress, and that the activation of the A10 cell body site (VTA) may precede that of the terminal field (MPFC). Moreover, diazepam was found to possess an inhibitory effect on the activation of mesoprefrontal DA neurons induced by psychological stress, and this effect may be partly mediated by benzodiazepine (BZD) receptors and implicated in the specific anxiolytic action of BZDs.