Tanda G, Bassareo V, Di Chiara G
Department of Toxicology, University of Cagliari, Italy.
Psychopharmacology (Berl). 1996 Jan;123(2):127-30. doi: 10.1007/BF02246169.
The atypical antidepressant mianserin, administered at doses of 1, 5 and 10 mg/kg SC, dose-dependently increased up to about 6 times extracellular dopamine in the medial prefrontal cortex of the rat, as estimated by vertical concentric microdialysis probes. Mianserin failed to modify extracellular dopamine in the nucleus accumbens. Mianserin also dose-dependently increased extracellular noradrenaline in the prefrontal cortex. Yohimbine, an alpha2 antagonist, increased extracellular dopamine in the prefrontal cortex but the maximal increase was lower than that elicited by mianserin. Yohimbine also increased extracellular noradrenaline in the prefrontal cortex, but to a lesser extent than dopamine. Clonidine, an alpha2 antagonist, decreased extracellular dopamine and noradrenaline in the prefrontal cortex but failed to affect extracellular dopamine in the nucleus accumbens. Ritanserin, a 5HT2 antagonist, at doses of 1.0 mg/kg, failed to increase extracellular dopamine in the prefrontal cortex, but significantly potentiated the increase 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 indicate that mianserin increases extracellular DA as a result of the concurrent blockade of alpha2 and 5HT2 receptors. Failure to affect extracellular dopamine in the nucleus accumbens is explained as due to the lack of a significant effect of alpha2 and 5HT2 tone on DA release in the nucleus accumbens as compared to the prefrontal cortex. The results are consistent with the postulated relationship between antidepressant drug action and the ability to increase extracellular dopamine in the prefrontal cortex.
非典型抗抑郁药米安色林，以1、5和10毫克/千克的剂量皮下注射，通过垂直同心微透析探针估计，能使大鼠内侧前额叶皮质的细胞外多巴胺剂量依赖性地增加至约6倍。米安色林未能改变伏隔核中的细胞外多巴胺。米安色林还能使前额叶皮质中的细胞外去甲肾上腺素剂量依赖性地增加。α2拮抗剂育亨宾能增加前额叶皮质中的细胞外多巴胺，但最大增加幅度低于米安色林引起的增加幅度。育亨宾也能增加前额叶皮质中的细胞外去甲肾上腺素，但幅度小于多巴胺。α2拮抗剂可乐定能降低前额叶皮质中的细胞外多巴胺和去甲肾上腺素，但未能影响伏隔核中的细胞外多巴胺。5HT2拮抗剂利坦色林，剂量为1.0毫克/千克，未能增加前额叶皮质中的细胞外多巴胺，但能显著增强育亨宾引起的细胞外去甲肾上腺素的增加。利坦色林未能增强育亨宾在前额叶皮质中引起的细胞外去甲肾上腺素的增加。这些结果被解释为表明米安色林增加细胞外多巴胺是由于同时阻断了α2和5HT2受体。未能影响伏隔核中的细胞外多巴胺被解释为与前额叶皮质相比，α2和5HT2张力对伏隔核中多巴胺释放缺乏显著影响。这些结果与抗抑郁药作用与增加前额叶皮质中细胞外多巴胺能力之间的假设关系一致。
