The selective attenuating effect of diazepam on yohimbine-induced increases in noradrenaline turnover in the amygdala of rats

Yohimbine, an alpha-2 adrenoceptor antagonist, has been reported to have anxiogenic action in human and animal studies. We have already reported that yohimbine causes increases in noradrenaline (NA) turnover in extended brain regions in rats. If these effects of yohimbine are related to its anxiogenic action, increased NA turnover in specific brain regions should be prevented by pretreatment with anxiolytics. In the present study, we investigated the effect of diazepam, One of the typical benzodiaze-pine anxiolytics, on yohimbine-induced increases in NA turnover in rat brain regions by measuring both levels of NA and its major metabolite, 3-methoxy-4-hydroxyphenyl-ethyleneglycol sulfate (MHPG-SO4 ). Male Wistar rats were injected twice with either diazepam (2.0 mg/kg×2, 5.0 mg/kg×2, i.p.) or vehicle at 5 min and 20 min before injection of yohimbine (0.5 mg/kg, s.c.). Each rat was decapitated 60 min after yohimbine treatment. Yohimbine caused increases in MHPG-SO4 levels in the hypothalamus, amygdala, locus coeruleus region, midbrain, cerebral cortex and hippocampus, and these changes accompanied decreases in NA levels in the hippocampus, cerebral cortex and amygdala. Diazepam at both doses attenuated increases in MHPG-SO4 levels induced by yohimbine only in the amygdala. These results suggest that the increases in NA turnover in the amygdala might be related to the production of anxiety by yohimbine.