Tapia Melissa A, Lee Jenna R, Bathe Emily L, Rivera Leticia L, Mason Kelsey L, Cessac Mikala E, Bodeen Jeffrey L, Miller Dennis K, Will Matthew J
Department of Psychological Sciences, University of Missouri, Columbia, MO, 65211, USA.
Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO, 65211, USA.
Behav Brain Res. 2019 Nov 5;373:112087. doi: 10.1016/j.bbr.2019.112087. Epub 2019 Jul 17.
Sigma-1 (σ) receptors have been investigated for their involvement in learning, rewarding and motivational processes. PD144418, a σ receptor antagonist, has been found to produce a dose-dependent attenuation of locomotor activity induced by cocaine, and by itself, does not suppress basal locomotor activity in mice. Moreover, PD144418 decreases the motivational effort of a food-reinforced behavior in male rats, without altering appetite or food palatability. It remains unknown whether the PD144418 can alter the motivational effort of a food-reinforced behavior in response to altered energy homeostasis, as is the case under 24 -h food deprivation. Additionally, while the previous experiments indicate effects in male rats, there has been no research examining the effects of PD144418, or any other σ receptor antagonist, on motivational aspects of feeding in females. The present study examined the effects of PD144418 on motivational aspects of feeding in male and female rats using an operant task under sated or food deprived conditions. Results indicated that when animals are sated, at the highest dose (10 μmol/kg), under a progressive ratio (PR) reinforcement schedule, PD144418 significantly attenuated the breakpoint and the number of active lever responses for sucrose pellets in both males and females. When animals are in a state of energy deficit, as is the case following 24-hr food deprivation, PD144418 does not alter motivationally driven operant responding as measured by the breakpoint in either sex but does alter the number of earned reinforcers responses in females.
西格玛-1（σ）受体因其在学习、奖赏和动机过程中的作用而受到研究。已发现σ受体拮抗剂PD144418能剂量依赖性地减弱可卡因诱导的小鼠运动活性，且其本身不会抑制小鼠的基础运动活性。此外，PD144418能降低雄性大鼠食物强化行为的动机努力，而不改变食欲或食物适口性。目前尚不清楚PD144418是否能像24小时食物剥夺情况下那样，响应能量稳态改变而改变食物强化行为的动机努力。另外，虽然先前的实验表明了对雄性大鼠的影响，但尚无研究考察PD144418或任何其他σ受体拮抗剂对雌性大鼠进食动机方面的影响。本研究使用操作性任务，在饱腹或食物剥夺条件下，考察了PD144418对雄性和雌性大鼠进食动机方面的影响。结果表明，当动物处于饱腹状态时，在累进比率（PR）强化程序下，最高剂量（10μmol/kg）的PD144418能显著减弱雄性和雌性大鼠获取蔗糖颗粒的断点及主动杠杆反应次数。当动物处于能量缺乏状态时，如24小时食物剥夺后，PD144418不会改变通过断点测量的任何性别动机驱动的操作性反应，但会改变雌性大鼠获得的强化物反应次数。
