Background

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.

Methods

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 During extinction, cocaine was withdrawn and the groups received daily mirtazapine (30 mg/kg, i.p.) or saline.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.

Results

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.

Conclusion

The results suggest that mirtazapine may be considered an effective therapeutic option for the treatment of cocaine use disorder in men and women.

中文翻译：

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米氮平降低雄性和雌性Wistar大鼠中可卡因诱导的运动敏化的表达。

背景

流行病学研究表明，妇女更容易受到可卡因的增强作用。在动物中，发现是相似的：雌性大鼠可卡因自我给药水平较高，可卡因诱导的自发活动增加。相反，患有抑郁症的妇女对抗抑郁药的治疗反应更好，但是她们对四环类抗抑郁药的治疗反应则较低。多项研究表明，米氮平是一种四环抗抑郁药，可降低可卡因在雄性大鼠中的行为作用。这项研究的目的是评估与雄性大鼠相比，每天服用米氮平对可卡因诱导的自发活动和敏化的功效。

方法

雄性和雌性Wistar大鼠每日服用10 mg / kg可卡因。灭绝期间，撤回可卡因，各组每天接受米氮平（30 mg / kg，腹膜内）或生理盐水。在拮抗阶段给予他莫昔芬。每次给药后，在透明的有机玻璃活动室中记录每只动物的运动活动30分钟。

结果

在这项研究中，发现雌性可卡因的运动反应比雄性要高，米氮平在降低可卡因诱导的运动能力和雄性和雌性大鼠运动敏感性的表达方面同样有效。另外，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功效。

结论

结果表明，米氮平可能被认为是治疗可卡因使用障碍的有效疗法。