We previously demonstrated that repeated exposure to the CB1 receptor antagonist/inverse agonist AM251 in adolescence (PND 30–44) increased social interactions in female rats when tested 48 h after the final exposure to the antagonist. Here, we investigated whether the increased sociality would be present after a longer drug washout period (5 days) in both male and female rats (experiment 1), and sought to identify candidate brain regions that may explain the observed differences in social behaviours between AM251 and vehicle‐treated female rats (experiment 2). While drug‐free, adolescent AM251 treatment increased social interactions in females and not in males. AM251 female rats had increased neural activity (as measured by the expression of early growth response protein‐1; EGR‐1) in the nucleus accumbens shell and cingulate gyrus of the medial prefrontal cortex, with no observed differences in EGR‐1 expression in the dorsal hippocampus, nucleus accumbens core, or prelimbic and infralimbic subdivisions of the medial prefrontal cortex relative to vehicle rats. Together, these results demonstrate a sex‐specific role of adolescent endocannabinoid signalling in the normative development of social behaviours and provide further support for adolescence as a vulnerable period for the effects of altered endocannabinoid signalling.

中文翻译：

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青春期 cb1 受体拮抗作用影响雌性大鼠随后的社会互动和神经活动

我们之前证明，在最终暴露于拮抗剂后 48 小时进行测试时，青春期反复暴露于 CB1 受体拮抗剂/反向激动剂 AM251（PND 30-44）会增加雌性大鼠的社交互动。在这里，我们调查了雄性和雌性大鼠（实验 1）在较长的药物清除期（5 天）后是否会出现增加的社交性，并试图确定可以解释观察到的 AM251 之间社交行为差异的候选大脑区域和载体处理的雌性大鼠（实验 2）。虽然没有药物，但青少年 AM251 治疗增加了女性而不是男性的社交互动。AM251 雌性大鼠的神经活动增加（通过早期生长反应蛋白-1 的表达来衡量；EGR-1) 在内侧前额叶皮层的伏隔核壳和扣带回中，与车辆大鼠相比，在背侧海马、伏隔核核心或内侧前额叶皮层的前缘和下缘细分中没有观察到 EGR-1 表达的差异. 总之，这些结果证明了青少年内源性大麻素信号在社会行为规范发展中的性别特异性作用，并进一步支持青春期是内源性大麻素信号改变影响的脆弱时期。