Borsoi Milene, Manduca Antonia, Bara Anissa, Lassalle Olivier, Pelissier-Alicot Anne-Laure, Manzoni Olivier J
Aix Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurobiologie de la Méditerranée (INMED), Marseille, France.
Cannalab, Cannabinoids Neuroscience Research International Associated Laboratory, INSERM-Indiana University, Marseille, France.
Front Behav Neurosci. 2019 Mar 5;13:23. doi: 10.3389/fnbeh.2019.00023. eCollection 2019.
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 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 exposure to cannabinoid at puberty and adulthood.
青少年大量吸食大麻会产生重大且持久的神经生物学、心理和健康后果，这些后果取决于首次使用的年龄。围产期或青春期长期接触大麻素激动剂会改变成年大鼠的社会行为和前额叶皮层（PFC）活动。然而，急性大麻素激活后社会行为以及PFC突触可塑性方面的性别差异仍未得到充分研究。在此，我们确定，在青春期和成年期，单次接触合成大麻素WIN55,212-2的后果在24小时后对雄性和雌性大鼠的PFC神经元和突触功能产生了不同影响。在青春期，单次大麻素暴露（SCE）减少了雌性大鼠的玩耍行为，但对雄性大鼠没有影响。相反，相同处理在成年期损害了两性的社交能力。在两个年龄段和两性中，一般探索和记忆识别均保持正常。在突触水平上，SCE消除了两个年龄段雌性大鼠PFC中内源性大麻素介导的突触可塑性，并在成年期增强了PFC锥体神经元的兴奋性，而雄性大鼠则未受影响。相反，大麻素暴露与成年雄性大鼠中特异性的长时程增强（LTP）受损有关。总之，这些数据表明在青春期和成年期单次接触大麻素后存在行为和突触方面的性别差异。
