Monoacylglycerol lipase inhibition alters social behavior in male and female rats after post-weaning social isolation.

Monoacylglycerol lipase inhibition alters social behavior in male and female rats after post-weaning social isolation.
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DOI:
10.1016/j.bbr.2017.12.038
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发表时间:
2018-04-02
影响因子:
2.7
通讯作者:
Bland ST
Bland ST
中科院分区:
心理学3区
文献类型:
--
作者:
Fontenot J;Loetz EC;Ishiki M;Bland ST

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断奶后社会隔离(PSI)已被证明会增加大鼠的攻击行为并改变内侧前额叶皮质(mPFC)功能。本研究试图通过药物抑制单酰基甘油脂肪酶(MAGL)来增加内源性大麻素2-花生四烯醇甘油(2-AG)水平,从而确定这种表型是否会正常化。雄性和雌性Sprague-Dawley大鼠从出生后第21天开始接受为期4周的PSI或社会饲养(SR),然后与一只新的同性幼鼠进行15分钟的社会互动试验。在社会互动之前,给大鼠急性注射MAGL抑制剂MJN110或载体。大鼠分别给予0 mg/kg(载药)、1 mg/kg或5 mg/kg的MJN110。两种剂量的MJN110都减少了雄性和雌性的攻击性梳理,这是一种激动行为的衡量标准,主要是由PSI大鼠的攻击性梳理减少引起的。MJN110对大鼠整体社交行为和游戏行为没有影响,仅对SR大鼠的运动活动有适度影响。虽然社会互动增加了男性和女性mPFC中c-fos的表达,但MJN110在女性中优先降低了c-fos的表达。这些结果表明,2-AG可以调节青春期特定的社会行为,并可能对男性和女性的mPFC功能产生不同的影响。
Post-weaning social isolation (PSI) has been shown to increase aggressive behavior and alter medial prefrontal cortex (mPFC) function in rats. The present study sought to determine whether this phenotype would be normalized by increasing levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) using pharmacological inhibition of monoacylglycerol lipase (MAGL). Male and female Sprague-Dawley rats were exposed to either 4 weeks of PSI or social rearing (SR) starting on postnatal day 21, then underwent a 15 min trial of social interaction with a novel, same-sex juvenile rat. Rats were administered an acute injection of the MAGL inhibitor MJN110 or vehicle prior to the social interaction. Rats received either 0 mg/kg (vehicle), 1 mg/kg, or 5 mg/kg of MJN110. Both doses of MJN110 decreased aggressive grooming, a measure of agonistic behavior, in both males and females, largely driven by decreased aggressive grooming in PSI rats. There were no effects of MJN110 on overall social behavior or play behavior, while modest effects were observed on locomotor activity in SR rats only. While social interaction increased c-fos expression in the mPFC of both males and females, MJN110 reduced c-fos preferentially in females. These results suggest that 2-AG can modulate specific social behaviors during adolescence, and may affect mPFC function differentially in males and females.
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