MIANSERIN MARKEDLY AND SELECTIVELY INCREASES EXTRACELLULAR DOPAMINE IN THE PREFRONTAL CORTEX AS COMPARED TO THE NUCLEUS-ACCUMBENS OF THE RAT

The atypical antidepressant mianserin, administered at doses of 1, 5 a nd 10 mg/kg SC, dose-dependently increased up to about 6 times extrace llular dopamine in the medial prefrontal cortex of the rat, as estimat ed by vertical concentric microdialysis probes. Mianserin failed to mo dify extracellular dopamine in the nucleus accumbens. Mianserin also d ose-dependently increased extracellular noradrenaline in the prefronta l cortex. Yohimbine, an alpha(2) antagonist, increased extracellular d opamine in the prefrontal cortex but the maximal increase was lower th an that elicited by mianserin. Yohimbine also increased extracellular noradrenaline in the prefrontal cortex, but to a lesser extent than do pamine. Clonidine, an alpha(2) agonist, decreased extracellular dopami ne and noradrenaline in the prefrontal cortex but failed to affect ext racellular dopamine in the nucleus accumbens. Ritanserin, a 5HT(2) ant agonist, at doses of 1.0 mg/kg, failed to increase extracellular dopam ine in the prefrontal cortex, but significantly potentiated the increa se in extracellular noradrenaline due to yohimbine. Ritanserin failed to potentiate the increase in extracellular noradrenaline elicited by yohimbine in the prefrontal cortex. The results are interpreted to ind icate that mianserin increases extracellular DA as a result of the con current blockade of alpha(2) and 5HT(2) receptors. Failure to affect e xtracellular dopamine in the nucleus accumbens is explained as due to the lack of a significant effect of alpha(2) and 5HT(2) tone on DA rel ease in the nucleus accumbens as compared to the prefrontal cortex. Th e results are consistent with the postulated relationship between anti depressant drug action and the ability to increase extracellular dopam ine in the prefrontal cortex.