Serafine Katherine M, Bentley Todd A, Grenier Amandine E, France Charles P
Departments of aPharmacology bPsychiatry, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Behav Pharmacol. 2014 Aug;25(4):287-95. doi: 10.1097/FBP.0000000000000052.
Eating high fat chow increases the sensitivity of male rats to some behavioral effects of the direct-acting dopamine receptor agonist quinpirole; it is not known whether sensitivity to quinpirole is similarly enhanced in female rats eating high fat chow. Female Sprague-Dawley rats had free access to standard chow (5.7% fat) or either free or restricted access (i.e. body weight matched to rats eating standard chow) to high fat (34.3% fat) chow. Quinpirole (0.0032-0.32 mg/kg) produced hypothermia and a low frequency of yawning. Eating high fat chow produced insulin resistance without affecting quinpirole-induced yawning or hypothermia. Pretreatment with the dopamine D2 receptor antagonist L-741,626 failed to increase quinpirole-induced yawning, indicating that the low frequency of yawning was not due to enhanced D2 receptor sensitivity. Compared with younger (postnatal day 75), drug-naive female rats in a previous study, rats in the present study (postnatal day 275) were more sensitive to cocaine-elicited (1-17.8 mg/kg) locomotion and the development of sensitization across 5 weeks; however, eating high fat chow did not further enhance these effects. These results suggest that drug history and age might modulate the effects of diet on sensitivity to drugs acting on dopamine systems.
食用高脂肪食物会增加雄性大鼠对直接作用的多巴胺受体激动剂喹吡罗某些行为效应的敏感性；尚不清楚食用高脂肪食物的雌性大鼠对喹吡罗的敏感性是否同样增强。雌性斯普拉格-道利大鼠可自由获取标准食物（脂肪含量5.7%），或自由或限量获取（即体重与食用标准食物的大鼠匹配）高脂肪（脂肪含量34.3%）食物。喹吡罗（0.0032 - 0.32毫克/千克）可导致体温过低和打哈欠频率降低。食用高脂肪食物会产生胰岛素抵抗，但不影响喹吡罗诱导的打哈欠或体温过低。用多巴胺D2受体拮抗剂L - 741,626预处理未能增加喹吡罗诱导的打哈欠，表明打哈欠频率低并非由于D2受体敏感性增强。与先前研究中未接触过药物的年轻（出生后第75天）雌性大鼠相比，本研究中的大鼠（出生后第275天）对可卡因诱发的（1 - 17.8毫克/千克）运动更敏感，且在5周内敏化作用的发展更明显；然而，食用高脂肪食物并未进一步增强这些效应。这些结果表明，用药史和年龄可能会调节饮食对作用于多巴胺系统药物敏感性的影响。
