Job Martin O, Kuhar Michael J
The Yerkes National Primate Research Center of Emory University, 954 Gatewood Rd NE, Atlanta, GA 30329, USA; Psychobiology Section, Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, Intramural Research Program, NIH, Baltimore, MD 21224, USA.
The Yerkes National Primate Research Center of Emory University, 954 Gatewood Rd NE, Atlanta, GA 30329, USA.
Neuroscience. 2017 Apr 21;348:135-142. doi: 10.1016/j.neuroscience.2017.02.012. Epub 2017 Feb 16.
In this study, we reexamined the effect of Cocaine-and-Amphetamine-Regulated-Transcript (CART) peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS-treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine-induced LMA, which supports our earlier homeostatic hypothesis.
在本研究中,我们重新审视了可卡因和苯丙胺调节转录肽(CART)对个体大鼠中精神兴奋剂(PS)诱导的运动活动(LMA)的影响。所采用的方法如先前发表的那样。PS诱导的LMA定义为PS给药(腹腔内)后行进的距离,而CART肽的作用定义为双侧伏隔核内注射CART肽后PS诱导活动的变化。实验包括雄性和雌性Sprague-Dawley大鼠,并改变CART肽剂量和PS剂量。虽然CART肽的平均作用是抑制PS诱导的LMA,但CART肽对个体PS处理动物的作用并不总是抑制性的,有时甚至会使PS诱导的LMA增加或无变化。进一步分析后,我们首次观察到PS诱导的LMA大小与CART肽作用之间存在线性相关性。由于CART肽在PS诱导的LMA较大时抑制它,而在其较小时增加PS诱导的LMA,因此该肽可被视为多巴胺诱导的LMA的稳态调节剂,这支持了我们早期的稳态假说。