Prevention of the stress-induced increase in frontal cortical dopamine efflux of freely moving rats by long-term treatment with antidepressant drugs

Use of antidepressant drugs in the treatment of anxiety disorders has recen tly increased due to the anxiolytic effect of some of these agents. Because dopaminergic transmission in the prefrontal cortex is sensitive to anxioge nic or stressful stimuli, the effects of two antidepressant drugs with diff erent mechanisms of action, imipramine and mirtazapine, on the response of rat cortical dopaminergic neurons to stress were investigated. A 2-week (bu t not single dose) administration of imipramine (10 mg/kg, i.p., twice dail y) or mirtazapine (10 mg/kg, i.p., once daily) reduced and completely antag onized, respectively, the increase in dopamine release in the prefrontal co rtex elicited by footshock stress, Long-term administration of imipramine o r mirtazapine had no marked effect on the stress-induced increases in the b rain or plasma concentrations of neuroactive steroids or corticosterone. An attenuation of the response of mesocortical dopaminergic neurons to stress induced by long-term treatment with antidepressants might contribute to th e anxiolytic effects of such drugs. (C) 2001 Elsevier Science B.V. All righ ts reserved.