D'Aquila Paolo S, Canu Silvia, Sardella Marco, Spanu Caterina, Serra Gino, Franconi Flavia
Dipartimento di Scienze del Farmaco, Università di Sassari bPharmacovigilance - Medical Department, Gentium SpA, Villa Guardia (CO), Italy.
Behav Pharmacol. 2010 Feb;21(1):21-8. doi: 10.1097/FBP.0b013e32833470a7.
Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women. The aim of this study was to investigate the possible role of dopamine on the antidepressant-like effect of allopregnanolone in a model of depression. Thus, we examined (i) the behaviour of female Sprague-Dawley rats in the forced swimming test during estrus and diestrus and their response to allopregnanolone treatment (0.5, 1 and 2 mg/kg), and (ii) the effect of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01 and 0.025 mg/kg) and raclopride (0.05 and 0.2 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the same experimental model. We failed to observe differences in depressive-like behaviour between estrous phases, and allopregnanolone administration in both estrus and diestrus resulted in an antidepressant-like effect consisting in an increase of swimming behaviour. The allopregnanolone effect was unaffected by a dose of the dopamine D1-like receptor antagonist SCH 23390 displaying a marked inhibitory effect on basal activity, while it was turned into a potentiation of the depressive-like behaviour of the forced swimming condition by treatment with the higher dose of raclopride. The present results indicate an involvement of dopamine transmission in the allopregnanolone antidepressant-like effect in the forced swimming model of depression, and suggest that this effect depends mainly on stimulation of dopamine D2-like receptors.
来自动物和人体研究的证据表明,多巴胺在抗抑郁药物的治疗效果中发挥作用。一直以来,多巴胺受体拮抗剂在不同的抑郁症实验模型中可拮抗抗抑郁药物的作用。神经甾体,尤其是别孕烯醇酮,似乎既参与抑郁症的病理生理学过程,也参与抗抑郁药物的作用机制,而且它们的作用在理解与女性生殖生活不同阶段相关的情绪障碍方面似乎尤为重要。本研究的目的是在抑郁症模型中探究多巴胺对别孕烯醇酮抗抑郁样作用的可能影响。因此,我们检测了:(i)雌性斯普拉格-道利大鼠在动情期和间情期强迫游泳试验中的行为表现以及它们对别孕烯醇酮治疗(0.5、1和2毫克/千克)的反应;(ii)多巴胺D1样和D2样受体拮抗剂SCH 23390(0.01和0.025毫克/千克)和雷氯必利(0.05和0.2毫克/千克)对同一实验模型中别孕烯醇酮(2毫克/千克)抗抑郁样作用的影响。我们未观察到动情期之间抑郁样行为的差异,并且在动情期和间情期给予别孕烯醇酮均产生了抗抑郁样作用,表现为游泳行为增加。别孕烯醇酮的作用不受对基础活动有显著抑制作用的多巴胺D1样受体拮抗剂SCH 23390剂量的影响,而用较高剂量的雷氯必利治疗则使其转变为强迫游泳条件下抑郁样行为的增强。目前的结果表明,多巴胺传递参与了别孕烯醇酮在抑郁症强迫游泳模型中的抗抑郁样作用,并提示该作用主要取决于对多巴胺D2样受体的刺激。