Kuiper Lindsey B, Frohmader Karla S, Coolen Lique M
Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, USA.
Graduate Program in Neuroscience, University of Mississippi Medical Center, Jackson, MS, USA.
Neuropsychopharmacology. 2017 Sep;42(10):2011-2020. doi: 10.1038/npp.2017.1. Epub 2017 Jan 4.
The use of psychostimulants is often associated with hypersexuality, and psychostimulant users have identified the effects of drug on sexual behavior as a reason for further use. It was previously demonstrated in male rats that methamphetamine (Meth), when administered concurrently with sexual behavior results in impairment of inhibition of sexual behavior in a conditioned sex aversion (CSA) paradigm where mating is paired with illness. This is indicative of maladaptive sex behavior following Meth and sex experience. The present study examined the neural pathways activated during inhibition of sexual behavior in male rats and the effects of concurrent Meth and sexual behavior on neural activity, using ERK phosphorylation (pERK). First, exposure to conditioned aversive stimuli in males trained to inhibit sexual behavior in the CSA paradigm increased pERK expression in medial prefrontal (mPFC), orbitofrontal cortex (OFC) and areas in striatum and amygdala. Second, effects of concurrent Meth and sex experience were tested in males that were exposed to four daily sessions of concurrent Meth (1 mg/kg) or saline and mating and subsequently exposed to CSA one week after last treatment. Meth and mating-treated males showed significant impairment of inhibition of mating, higher pERK expression under baseline conditions, and disrupted pERK induction by exposure to the conditioned aversive stimuli in mPFC and OFC. These alterations of pERK occurred in CaMKII-expressing neurons, suggesting changes in efferent projections of these areas. Altogether, these data show that concurrent Meth and mating experience causes maladapative sexual behavior that is associated with alterations in neural activation in mPFC and OFC.
使用精神兴奋剂常常与性欲亢进相关，并且精神兴奋剂使用者已将药物对性行为的影响认定为进一步使用药物的一个原因。先前在雄性大鼠中已证实，在条件性性厌恶（CSA）范式（即交配与疾病配对）中，当同时给予性行为时，甲基苯丙胺（冰毒）会导致性行为抑制受损。这表明冰毒和性经历后存在适应不良的性行为。本研究使用细胞外信号调节激酶磷酸化（pERK），检测了雄性大鼠在抑制性行为期间激活的神经通路，以及同时给予冰毒和性行为对神经活动的影响。首先，在CSA范式中接受训练以抑制性行为的雄性大鼠暴露于条件性厌恶刺激后，内侧前额叶（mPFC）、眶额皮质（OFC）以及纹状体和杏仁核区域的pERK表达增加。其次，对每天接受四次冰毒（1毫克/千克）或生理盐水与交配同时处理，然后在最后一次处理一周后接受CSA的雄性大鼠，测试同时给予冰毒和性经历的影响。接受冰毒和交配处理的雄性大鼠在抑制交配方面表现出显著受损，在基线条件下pERK表达更高，并且在mPFC和OFC中暴露于条件性厌恶刺激后pERK诱导受到破坏。这些pERK的改变发生在表达钙/钙调蛋白依赖性蛋白激酶II（CaMKII）的神经元中，表明这些区域的传出投射发生了变化。总之，这些数据表明，同时给予冰毒和交配经历会导致适应不良的性行为，这与mPFC和OFC中的神经激活改变有关。
