The Anxiogenic Agents, Yohimbine and FG 7142, Disrupt the Noradrenergic Response to Novelty

Whether or not abnormal noradrenergic transmission can be a causal factor in anxiety is controversial. The present experiments examined this question by comparing the effects of two anxiogenic agents on noradrenaline efflux in the frontal cortex of freely moving rats. A single anxiogenic dose of either yohimbine (2.5 or 5 mg/kg) or FG 7142 (10 or 20 mg/kg) was administered to rats by i.p. injection. Yohimbine increased spontaneous efflux of noradrenaline, but FG 7142 had no effect. However, subsequent exposure of rats to a novel environment increased noradrenaline efflux in vehicle-, but not drug-treated rats. Calculation of the net change in noradrenaline efflux caused by transfer to the novel environment showed that this was reduced by yohimbine, whereas FG 7142 increased it. These two compounds also had different effects on locomotor activity in the novel environment. The results suggest that anxiety is unlikely to be invariably associated with increased noradrenergic transmission, in the frontal cortex at least. However, it remains possible that any disruption of the noradrenergic response to stress could be an underlying feature of anxiety.