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性活跃的青春期雌性大鼠对可卡因作用的敏感性降低及中脑皮质边缘多巴胺受体的变化

Reduced sensitivity to cocaine effects and changes in mesocorticolimbic dopamine receptors in adolescent sexually active female rats.

作者信息

Agrati Daniella, Marin Gabriella, Rehermann Lucía, Uriarte Natalia, Antonelli Marta C, Bedó Gabriela

机构信息

Physiology and Nutrition Department, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.

Basic Nutrition Department, Escuela de Nutrición, Universidad de la República, Montevideo, Uruguay.

出版信息

Psychopharmacology (Berl). 2025 Apr;242(4):817-834. doi: 10.1007/s00213-024-06741-3. Epub 2024 Dec 27.

Abstract

RATIONALE

The sexual behavior of the female rat is highly motivated, and the mesocorticolimbic dopaminergic system -involved in psychostimulants effects- has been implicated in its regulation. Female rats begin to express sexual behavior during adolescence, a period during which this system is not yet mature.

OBJECTIVE

To examine the impact of cocaine on sexual motivation and behavior of adolescent and adult female rats, and to determine the dopamine receptors binding in mesocorticolimbic areas of these females.

METHODS

The effect of acute administration of cocaine (0.0, 10.0, and 20.0 mg/kg, intraperitoneally) on the male´s incentive value for females and on their sexual behavior in late adolescent (45-55 days old) and adult (100-120 days old) rats was assessed during late proestrus. The binding of D1-like and D2-like receptors in the striatum and medial prefrontal cortex (mPFC) of adolescent and adult rats were determined by autoradiography.

RESULTS

Cocaine did not affect females´ preference for the male. However, 10 mg/kg of cocaine reduced the expression of sexual motivated responses and 20 mg/kg also diminished sexual receptivity exclusively in adult subjects. Moreover, cocaine-induced a more pronounced hyper-locomotion in adult than in late adolescent rats. Late adolescent females exhibited higher dopamine receptors binding in the mPFC and reduced D2-like receptors binding in the Nucleus Accumbens shell when compared to adults.

CONCLUSIONS

Late adolescent females are less sensitive than adults to the detrimental effects of cocaine on sexual behavior and locomotion. This phenomenon is accompanied by variation in dopamine receptors in mesocorticolimbic areas affected by this psychostimulant.

摘要

理论依据

雌性大鼠的性行为动机强烈,参与精神兴奋剂作用的中脑皮质边缘多巴胺能系统已被证实与性行为调节有关。雌性大鼠在青春期开始表现出性行为,而在此期间该系统尚未成熟。

目的

研究可卡因对青春期和成年雌性大鼠性动机及性行为的影响,并确定这些雌性大鼠中脑皮质边缘区域的多巴胺受体结合情况。

方法

在动情后期,评估急性腹腔注射可卡因(0.0、10.0和20.0毫克/千克)对青春期后期(45 - 55日龄)和成年(100 - 120日龄)大鼠中雄性对雌性的吸引力以及雌性性行为的影响。通过放射自显影法测定青春期和成年大鼠纹状体及内侧前额叶皮质(mPFC)中D1样和D2样受体的结合情况。

结果

可卡因不影响雌性对雄性的偏好。然而,10毫克/千克的可卡因降低了性动机反应的表达,且20毫克/千克的可卡因仅在成年大鼠中降低了性接受能力。此外,可卡因在成年大鼠中诱导的运动亢进比青春期后期大鼠更明显。与成年大鼠相比,青春期后期雌性大鼠mPFC中的多巴胺受体结合较高,伏隔核壳中的D2样受体结合减少。

结论

青春期后期雌性大鼠对可卡因在性行为和运动方面的有害影响比成年大鼠更不敏感。这种现象伴随着受这种精神兴奋剂影响的中脑皮质边缘区域多巴胺受体的变化。

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