Animal models suggest that the endocannabinoid system (eCS) helps regulate various aspects of social behavior, including play behavior and social reward, during adolescence. Properly tuned endocannabinoid signaling may be a critical developmental component in the emergence of normal adult sociability. In the current experiment, we attempted to pharmacologically disrupt endocannabinoid tone during early adolescence, and then measure the behavioral effects at two subsequent time points. 36 male and 36 female Long Evans rats received daily injections of one of three treatments between post-natal day (PND) 25–39: 1) vehicle treatment, 2) 0.4 mg/kg CP55,940 (a potent CB1/CB2 receptor agonist), or 3) 0.5 mg/kg AM251 (a CB1 receptor antagonist/inverse agonist). Both soon after treatment (PND 40–44) and several weeks later (PND 66–70), subjects were tested in an elevated plus maze (EPM) for anxiety and in a three-chambered apparatus for sociability. For the latter test, the number of entries into each chamber and the amount of time spent investigating each target were measured. Analyses revealed significant main effects of both sex and age on sociability: males expressed greater sociability compared to females, and sociability was higher in adolescence than adulthood. Most importantly, drug treatment (both CP55,940 and AM251) attenuated sociability in adolescence without having a significant effect on anxiety in the EPM. However, this effect did not persist into adulthood. These results indicate that pharmacological disruption of endocannabinoid tone – through either chronic agonism or antagonism of cannabinoid receptors - during early adolescence has a detrimental effect on sociability. This effect may be caused by transient, compensatory alterations in the eCS.

动物模型表明，内源性大麻素系统（eCS）有助于调节青春期社交行为的各个方面，包括游戏行为和社交奖励。正确调节的内源性大麻素信号可能是正常成人社交能力出现的关键发展因素。在当前的实验中，我们尝试在药理学上扰乱青春期早期的内源性大麻素，然后在随后的两个时间点测量行为影响。在出生后一天（PND）25-39之间，每天对36只雄性和36只雌性Long Evans大鼠进行三种治疗之一的每日注射：1）媒介物治疗； 2）0.4 mg / kg CP55,940（一种有效的CB1 / CB2受体激动剂） ）或3）0.5 mg / kg AM251（一种CB1受体拮抗剂/反向激动剂）。在治疗后不久（PND 40-44）和几周后（PND 66-70），受试者在高架迷宫（EPM）中进行焦虑测试，并在三室仪器中进行社交测试。对于后面的测试，测量进入每个小室的次数以及研究每个目标所花费的时间。分析显示，性别和年龄对社交能力都有重要的主要影响：男性比女性表现出更高的社交能力，青春期的社交能力比成年期更高。最重要的是，药物治疗（CP55,940和AM251）都降低了青春期的社交能力，而对EPM的焦虑没有显着影响。但是，这种作用并没有持续到成年期。这些结果表明，在青春期早期，通过对大麻素受体的慢性激动或拮抗作用，破坏内源性大麻素的音调会对社交能力产生不利影响。这种影响可能是由eCS中的瞬时补偿性变化引起的。