Sex Differences in the Behavioral and Synaptic Consequences of a Single in vivo Exposure to the Synthetic Cannabimimetic WIN55,212-2 at Puberty and Adulthood
Sex Differences in the Behavioral and Synaptic Consequences of a Single in vivo Exposure to the Synthetic Cannabimimetic WIN55,212-2 at Puberty and Adulthood
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DOI：
10.3389/fnbeh.2019.00023
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发表时间：
2019-03-05
影响因子：
3
通讯作者：
Manzoni, Olivier J.
中科院分区：
文献类型：
--
作者：
Borsoi, Milene;Manduca, Antonia;Manzoni, Olivier J.
青少年大量吸食大麻与重大和持久的神经生物学、心理和健康后果有关，这些后果取决于首次使用大麻的年龄。围产期或青春期长期暴露于大麻类激动剂会改变成年大鼠的社会行为和前额叶皮质(PFC)活动。然而，社会行为的性别差异以及急性大麻素激活后PFC突触可塑性的研究仍然很少。在这里，我们确定了在青春期和成年期，单次体内暴露于合成的拟大麻化合物WIN55,212-2对24小时后雄性和雌性大鼠的PFC神经元和突触功能的影响不同。在青春期，单一的大麻素暴露(SCE)减少了女性的游戏行为，但男性没有。相比之下，同样的待遇会在成年后损害两性的社交能力。一般探索和记忆识别在年龄和性别上都是正常的。在突触水平上，姐妹染色单体交换抑制了两个年龄段女性PFC内大麻素介导的突触可塑性，增强了成年后PFC锥体神经元的兴奋性，而男性则不受影响。相比之下，暴露于大麻类物质与长时程增强(LTP)受损有关，特别是在成年男性。总之，这些数据表明，在青春期和成年期，行为和突触性别对单一体内暴露于大麻类药物的反应存在差异。
Heavy cannabis consumption among adolescents is associated with significant and lasting neurobiological, psychological and health consequences that depend on the age of first use. Chronic exposure to cannabinoid agonists during the perinatal period or adolescence alters social behavior and prefrontal cortex (PFC) activity in adult rats. However, sex differences on social behavior as well as PFC synaptic plasticity after acute cannabinoid activation remain poorly explored. Here, we determined that the consequences of a single in vivo exposure to the synthetic cannabimimetic WIN55,212-2 differently affected PFC neuronal and synaptic functions after 24 h in male and female rats during the pubertal and adulthood periods. During puberty, single cannabinoid exposure (SCE) reduced play behavior in females but not males. In contrast, the same treatment impaired sociability in both sexes at adulthood. General exploration and memory recognition remained normal at both ages and both sexes. At the synaptic level, SCE ablated endocannabinoid-mediated synaptic plasticity in the PFC of females of both ages and heightened excitability of PFC pyramidal neurons at adulthood, while males were spared. In contrast, cannabinoid exposure was associated with impaired long-term potentiation (LTP) specifically in adult males. Together, these data indicate behavioral and synaptic sex differences in response to a single in vivo exposure to cannabinoid at puberty and adulthood.