Hamilton John, Marion Matthew, Figueiredo Antonio, Clavin Brendan H, Deutsch Dale, Kaczocha Martin, Haj-Dahmane Samir, Thanos Panayotis K
Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, New York.
Department of Biochemistry, Stony Brook University, Stony Brook, New York.
Synapse. 2018 Jun;72(6):e22031. doi: 10.1002/syn.22031. Epub 2018 Feb 19.
Genetic and pharmacological manipulation of endocannabinoid (eCB) signaling has previously been shown to have an important role on the rewarding properties of drugs of abuse, including cocaine. Recently, fatty acid binding proteins (FABPs) have been proposed as intracellular transporters of the endocannabinoid anandamide (AEA) as well as other bioactive lipids to their catabolic enzyme, fatty acid amide hydrolase (FAAH). The role of these transporters in modulating the brains reward system has yet to be investigated. This study examined the effects of genetic deletion of FABP 5/7 on cocaine preference, as assessed by the Conditioned Place Preference (CPP) paradigm. Male and female wild type (WT) and FABP 5/7 KO mice showed similar acquisition of cocaine CPP, with no differences found in overall locomotor activity. In addition, while male and female WT mice showed stress-induced CPP for cocaine, male and female FABP 5/7 KO mice failed to show a stress-induced preference for the cocaine-paired chamber. Additionally, serum corticosterone levels were analyzed to explore any potential differences in stress response that may be responsible for the lack of stress-induced preference for cocaine. Serum samples were obtained in animals under basal conditions as well as following a 30-min tube restraint stress. Male and female FABP 5/7 KO mice showed reduced corticosterone levels under stress compared to their WT counterparts. The reduction in corticosterone response under stress may mediate that lack of a stress-induced preference for cocaine in the FABP 5/7 KO mice. Thus, the role of FABPs may play an important role in drug-seeking behavior under stressful conditions.
先前已证明，对内源性大麻素（eCB）信号通路进行基因和药理学操作，对包括可卡因在内的滥用药物的奖赏特性具有重要作用。最近，脂肪酸结合蛋白（FABP）被认为是内源性大麻素花生四烯酸乙醇胺（AEA）以及其他生物活性脂质的细胞内转运蛋白，可将它们转运至分解代谢酶脂肪酸酰胺水解酶（FAAH）。这些转运蛋白在调节大脑奖赏系统中的作用尚待研究。本研究通过条件性位置偏爱（CPP）范式，检测了FABP 5/7基因敲除对可卡因偏爱性的影响。雄性和雌性野生型（WT）及FABP 5/7基因敲除小鼠在可卡因CPP获得方面表现相似，总体运动活性未发现差异。此外，虽然雄性和雌性WT小鼠表现出应激诱导的对可卡因的CPP，但雄性和雌性FABP 5/7基因敲除小鼠未表现出对应激诱导的对与可卡因配对腔室的偏爱。另外，分析血清皮质酮水平，以探究可能导致缺乏应激诱导的对可卡因偏爱的应激反应中的任何潜在差异。在基础条件下以及30分钟的管束缚应激后，采集动物的血清样本。与WT同窝小鼠相比，雄性和雌性FABP 5/7基因敲除小鼠在应激状态下的皮质酮水平降低。应激状态下皮质酮反应的降低可能介导了FABP 5/7基因敲除小鼠缺乏应激诱导的对可卡因的偏爱。因此，FABP可能在应激条件下的觅药行为中起重要作用。
