Barbosa-Méndez Susana, Salazar-Juárez Alberto
Subdirección de Investigaciones Clínicas, Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Instituto Nacional de Psiquiatría, Ciudad de México, Mexico.
Front Psychiatry. 2024 Aug 12;15:1428730. doi: 10.3389/fpsyt.2024.1428730. eCollection 2024.
Chronic cocaine exposure induces an increase in dopamine release and an increase in the expression of the Fos protein in the rat striatum. It has been suggested that both are necessary for the expression of cocaine-induced alterations in behavior and neural circuitry. Mirtazapine dosing attenuated the cocaine-induced psychomotor and reinforcer effects.
The study evaluates the effect of chronic dosing of mirtazapine on cocaine-induced extracellular dopamine levels and Fos protein expression in rats. Male Wistar rats received cocaine (10 mg/Kg; i.p.) during the induction and expression of locomotor sensitization. The mirtazapine (30 mg/Kg; MIR), was administered 30 minutes before cocaine during the cocaine withdrawal. After each treatment, the locomotor activity was recorded for 30 minutes. Animals were sacrificed after treatment administration. Dopamine levels were determined by high-performance liquid chromatographic (HPLC) in the ventral striatum, the prefrontal cortex (PFC), and the ventral tegmental area (VTA) in animals treated with mirtazapine and cocaine. The quantification of c-fos immunoreactive cells was carried out by stereology analysis.
Mirtazapine generated a decrease in cocaine-induced locomotor activity. In addition, mirtazapine decreased the amount of cocaine-induced dopamine and the number of cells immunoreactive to the Fos protein in the striatum, PFC, and VTA.
These data suggest that mirtazapine could prevent the consolidation of changes in behavior and the cocaine-induced reorganization of neuronal circuits. It would explain the mirtazapine-induced effects on cocaine behavioral sensitization. Thus, these data together could support its possible use for the treatment of patients with cocaine use disorder.
长期接触可卡因会导致大鼠纹状体中多巴胺释放增加以及Fos蛋白表达增加。有人认为，这两者对于可卡因诱导的行为和神经回路改变的表达都是必要的。米氮平给药可减弱可卡因诱导的精神运动和强化作用。
本研究评估了长期给予米氮平对可卡因诱导的大鼠细胞外多巴胺水平和Fos蛋白表达的影响。雄性Wistar大鼠在运动敏化的诱导和表达过程中接受可卡因（10毫克/千克；腹腔注射）。在可卡因戒断期间，于给予可卡因前30分钟给予米氮平（30毫克/千克；MIR）。每次治疗后，记录30分钟的运动活动。给药后处死动物。采用高效液相色谱法（HPLC）测定给予米氮平和可卡因的动物腹侧纹状体、前额叶皮质（PFC）和腹侧被盖区（VTA）中的多巴胺水平。通过体视学分析对c-fos免疫反应性细胞进行定量。
米氮平使可卡因诱导的运动活动减少。此外，米氮平降低了可卡因诱导的纹状体、PFC和VTA中的多巴胺量以及Fos蛋白免疫反应性细胞的数量。
这些数据表明，米氮平可以预防行为变化的巩固和可卡因诱导的神经回路重组。这可以解释米氮平对可卡因行为敏化的诱导作用。因此，这些数据共同支持其可能用于治疗可卡因使用障碍患者。
