Department of Psychiatry, Ribicoff Research Facilities, Yale University School of Medicine, 34 Park St.-CMHC, New Haven, CT 06519, USA.
Brain Res. 2010 Mar 4;1317:24-32. doi: 10.1016/j.brainres.2009.12.035. Epub 2009 Dec 23.
Orexin (or hypocretin) has been implicated in mediating drug addiction and reward. Here, we investigated orexin's contribution to morphine-induced behavioral sensitization and place preference. Orexin-/- (OKO) mice and littermate wild-type (WT) controls (n=56) and C57BL/6J mice (n=67) were tested for chronic morphine-induced locomotor sensitization or for conditioned place preference (CPP) for a morphine- or a cocaine-paired environment. C57BL/6J mice received the orexin receptor 1 (Ox1r) antagonist, SB-334867, prior to test sessions. OKO mice did not significantly differ from WT controls in locomotor activity following acute- or chronic-morphine treatments. Similarly, mice treated with the Ox1r antagonist did not differ from vehicle controls in locomotor activity following acute- or chronic-morphine treatments. In contrast, while OKO mice did not differ from WT controls in preference for a morphine-paired environment, the Ox1r antagonist significantly attenuated place preference for a morphine-, but not a cocaine-paired, environment. These data suggest that orexin action is not required for locomotor responses to acute and chronic morphine, but Ox1r signaling can influence morphine-seeking in WT animals.
食欲素（或下丘脑泌素）被认为在介导药物成瘾和奖赏中发挥作用。在这里，我们研究了食欲素在吗啡诱导的行为敏化和位置偏好中的作用。食欲素-/-（OKO）小鼠及其同窝野生型（WT）对照（n=56）和 C57BL/6J 小鼠（n=67）接受了慢性吗啡诱导的运动敏化或吗啡或可卡因配对环境的条件性位置偏好（CPP）测试。在测试前，C57BL/6J 小鼠接受了食欲素受体 1（Ox1r）拮抗剂 SB-334867 的处理。OKO 小鼠在急性或慢性吗啡处理后，其运动活性与 WT 对照相比没有显著差异。同样，在急性或慢性吗啡处理后，接受 Ox1r 拮抗剂处理的小鼠与载体对照相比，其运动活性没有差异。相比之下，虽然 OKO 小鼠在对吗啡配对环境的偏好上与 WT 对照没有差异，但 Ox1r 拮抗剂显著减弱了对吗啡而不是可卡因配对环境的偏好。这些数据表明，食欲素作用对于急性和慢性吗啡的运动反应不是必需的，但是 Ox1r 信号可以影响 WT 动物对吗啡的寻求。
