Kuiper Lindsey B, Lucas Kathryn A, Mai Vy, Coolen Lique M
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, United States.
Brain Health Research Institute, Kent State University, Kent, OH, United States.
Front Behav Neurosci. 2020 Jun 25;14:87. doi: 10.3389/fnbeh.2020.00087. eCollection 2020.
Individual variance in vulnerability to develop addictions is influenced by social factors. Specifically, drug-taking in a sexual context appears to enhance further drug-seeking behavior in human users, as these users identify the effects of drugs to enhance sexual pleasure as a primary reason for continued drug use. Methamphetamine (Meth) is commonly used in this context. Similarly, male rats that self-administered Meth immediately followed by sexual behavior display enhanced drug-seeking behavior, including attenuation of extinction and increased reinstatement to seeking of Meth-associated cues. Hence, drug-taking in a sexual context enhances vulnerability for addiction. However, the neural mechanisms by which this occurs are unknown. Here the hypothesis was tested that medial prefrontal cortex is essential for this effect of Meth and sex when experienced concurrently. First it was shown that CaMKII neurons in the anterior cingulate area (ACA) were co-activated by both Meth and sex. Next, chemogenetic inactivation of ACA CaMKII cells using AAV5-CaMKIIa-hM4Di-mCherry was shown not to affect Meth-induced locomotor activity or sexual behavior. Subsequently, chemogenetic inactivation of ACA CaMKII neurons during Meth self-administration followed by sexual behavior was shown to prevent the effects of Meth and sex on enhanced reinstatement of Meth-seeking but did not affect enhanced drug-seeking during extinction tests. These results indicate that ACA CaMKII cell activation during exposure to Meth in a sexual context plays an essential role in the subsequent enhancement of drug-seeking during reinstatement tests.
个体对成瘾易感性的差异受社会因素影响。具体而言，在性情境中吸毒似乎会进一步增强人类使用者的觅药行为，因为这些使用者将毒品增强性快感的效果视为持续吸毒的主要原因。甲基苯丙胺（冰毒）常用于这种情境。同样，自行注射冰毒后立即进行性行为的雄性大鼠表现出增强的觅药行为，包括消退减弱和对与冰毒相关线索寻求的复吸增加。因此，在性情境中吸毒会增加成瘾的易感性。然而，其发生的神经机制尚不清楚。在此，我们测试了内侧前额叶皮质对于冰毒和性行为同时出现时这种作用至关重要的假说。首先表明，前扣带区（ACA）的CaMKII神经元会被冰毒和性行为共同激活。接下来，使用AAV5-CaMKIIa-hM4Di-mCherry对ACA CaMKII细胞进行化学遗传学失活，结果显示这并不影响冰毒诱导的运动活动或性行为。随后，在冰毒自我给药后进行性行为期间对ACA CaMKII神经元进行化学遗传学失活，结果显示可防止冰毒和性行为对冰毒寻求复吸增强的影响，但不影响消退试验期间增强的觅药行为。这些结果表明，在性情境中接触冰毒期间ACA CaMKII细胞的激活在随后复吸试验中觅药行为的增强中起重要作用。
