Subdirección de Investigaciones Clínicas, Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Instituto Nacional de Psiquiatría, Ciudad de México 14370. Mexico.
Subdirección de Investigaciones Clínicas, Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Instituto Nacional de Psiquiatría, Ciudad de México 14370. Mexico.
Horm Behav. 2020 Sep;125:104817. doi: 10.1016/j.yhbeh.2020.104817. Epub 2020 Jul 23.
Epidemiological studies have described that women are more vulnerable to the reinforcing effects of cocaine. In animals, the findings are similar: female rats show higher levels of cocaine self-administration and increased cocaine-induced locomotor activity. In contrast, women with depression respond better to treatment with antidepressants, however their therapeutic response to tetracyclic antidepressants is lower. Several studies have shown that mirtazapine-a tetracyclic antidepressant-decreases the behavioral effects of cocaine in male rats. The objective of this study was to evaluate the efficacy of daily dosing of mirtazapine on cocaine-induced locomotor activity and sensitization in naive female rats compared to male rats.
Male and female Wistar rats were daily dosed with 10 mg/kg of cocaine. During extinction, cocaine was withdrawn and the groups received daily mirtazapine (30 mg/kg, i.p.) or saline. Tamoxifen was administered during the antagonism phase. After each administration, locomotor activity for each animal was recorded for 30 min in transparent Plexiglass activity chambers.
In this study, a higher cocaine locomotor response was found in females than in males and the mirtazapine was equally effective in decreasing cocaine-induced locomotor activity and the expression of locomotor sensitization in male and female rats. In addition, co-administration of mirtazapine and tamoxifen enhanced the efficacy of mirtazapine in female rats.
The results suggest that mirtazapine may be considered an effective therapeutic option for the treatment of cocaine use disorder in men and women.
流行病学研究表明，女性更容易受到可卡因的强化作用的影响。在动物中，研究结果相似：雌性大鼠表现出更高水平的可卡因自我给药和可卡因诱导的运动活动增加。相比之下，患有抑郁症的女性对抗抑郁药的治疗反应更好，然而，她们对四环抗抑郁药的治疗反应较低。几项研究表明，米氮平——一种四环抗抑郁药——可降低雄性大鼠可卡因的行为效应。本研究的目的是评估米氮平每日剂量对与雄性大鼠相比，对可卡因诱导的运动活动和敏化作用的疗效。
雄性和雌性 Wistar 大鼠每日给予 10mg/kg 的可卡因。在消除期，停止给予可卡因，各组给予每日米氮平（30mg/kg，ip）或生理盐水。在拮抗期给予他莫昔芬。每次给药后，在透明 plexiglass 活动室中记录每个动物的运动活动 30 分钟。
在这项研究中，发现雌性大鼠的可卡因运动反应高于雄性大鼠，米氮平同样有效降低了可卡因诱导的运动活动和运动敏化的表达在雄性和雌性大鼠中。此外，米氮平和他莫昔芬的共同给药增强了米氮平在雌性大鼠中的疗效。
结果表明，米氮平可被认为是治疗男性和女性可卡因使用障碍的有效治疗选择。
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