Cason Angie M, Aston-Jones Gary
Department of Neurosciences, Medical University of South Carolina, Basic Science Building 406, 173 Ashley Avenue, MSC 510, Charleston, SC 29425, USA.
Department of Neurosciences, Medical University of South Carolina, Basic Science Building 406, 173 Ashley Avenue, MSC 510, Charleston, SC 29425, USA.
Neuropharmacology. 2014 Nov;86:97-102. doi: 10.1016/j.neuropharm.2014.07.007. Epub 2014 Jul 15.
The orexin/hypocretin system has recently been implicated in reward-seeking, especially for highly salient food and drug rewards. Given that eating disorders affect women more than men, we reasoned that the orexin system may be strongly engaged in female rats, and during periods of food restriction as we recently reported in male rats. Therefore, the present study examined the involvement of the orexin system in operant responding for sucrose, and in cue-induced reinstatement of extinguished sucrose-seeking, in ad libitum fed vs. food-restricted female subjects. Female Sprague Dawley rats were trained to self-administer sucrose pellets, and we determined the effects of pretreatment with the OxR1 receptor antagonist SB 334867 (SB; 10-30 mg/kg) on fixed ratio (FR) sucrose self-administration, and on cue-induced reinstatement of extinguished sucrose-seeking. SB decreased sucrose self-administration in food-restricted but not in ad libitum-fed females. SB did not alter active lever responding during cue-induced reinstatement of sucrose-seeking in either feeding group. These results confirm our previous results in male rats that signaling at the OxR1 receptor is involved in the sucrose reinforcement and self-administration in food-restricted subjects. However, the finding that SB is ineffective at attenuating cue-induced reinstatement in females, but was effective in food-restricted males, leads us to conclude that food seeking induced by conditioned stimuli engages the orexin system differentially in males and females.
食欲素/下丘脑泌素系统最近被认为与寻求奖励有关，尤其是对于高度显著的食物和药物奖励。鉴于饮食失调对女性的影响大于男性，我们推测食欲素系统在雌性大鼠中可能会被强烈激活，正如我们最近在雄性大鼠中所报道的那样，在食物限制期间也是如此。因此，本研究考察了食欲素系统在自由进食与食物限制的雌性实验对象中，对蔗糖操作性反应以及线索诱导的消退蔗糖寻求行为恢复的影响。雌性斯普拉格-道利大鼠被训练自行摄取蔗糖颗粒，我们测定了用食欲素受体1（OxR1）拮抗剂SB 334867（SB；10 - 30毫克/千克）预处理对固定比率（FR）蔗糖自行摄取以及线索诱导的消退蔗糖寻求行为恢复的影响。SB降低了食物限制组雌性大鼠的蔗糖自行摄取量，但对自由进食组雌性大鼠没有影响。在两个进食组中，SB均未改变线索诱导的蔗糖寻求行为恢复过程中的主动杠杆反应。这些结果证实了我们之前在雄性大鼠中的研究结果，即OxR1受体信号传导参与了食物限制实验对象的蔗糖强化和自行摄取过程。然而，SB在减弱雌性大鼠线索诱导的行为恢复方面无效，但在食物限制的雄性大鼠中有效，这一发现使我们得出结论，条件刺激诱导的食物寻求行为在雄性和雌性大鼠中对食欲素系统的激活存在差异。
