Inhibition of stress- or anxiogenic-drug-induced increases in dopamine release in the rat prefrontal cortex by long-term treatment with antidepressant drugs

The effects of long-term treatment with imipramine or mirtazapine, two anti depressant drugs with different mechanisms of action, on the response of co rtical dopaminergic neurons to foot-shock stress or to the anxiogenic drug FG7142 were evaluated in freely moving rats. As expected, foot shock induce d a marked increase (+90%) in the extracellular concentration of dopamine i n the prefrontal cortex of control rats. Chronic treatment with imipramine or mirtazapine inhibited or prevented, respectively, the effect of foot-sho ck stress on cortical dopamine output. Whereas acute administration of the anxiogenic drug FG7142 induced a significant increase (+60%) in cortical do pamine output in control rats, chronic treatment with imipramine or mirtaza pine completely inhibited this effect. In contrast, the administration of a single dose of either antidepressant 40 min before foot shock, had no effe ct on the response of the cortical dopaminergic innervation to stress. Thes e results show that long-term treatment with imipramine or mirtazapine inhi bits the neurochemical changes elicited by stress or an anxiogenic drug wit h an efficacy similar to that of acute treatment with benzodiazepines. Give n that episodes of anxiety or depression are often preceded by stressful ev ents, modulation by antidepressants of the dopaminergic response to stress might be related to the anxiolytic and antidepressant effects of these drug s.