The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.

据报道，青春期摄入合成大麻素是日后出现精神疾病的一个危险因素。JWH-018 被确定为 Spice/K2 制剂中存在的主要精神活性成分之一。本研究评估了在青春期接触 JWH-018 对雄性和雌性小鼠的焦虑样行为、恐惧消退和感觉运动门控的短期和长期后果。焦虑的改变取决于治疗和行为分析之间的时间间隔以及性别，而恐惧记忆的消失没有观察到变化。在短期和长期的雄性小鼠而非雌性小鼠中，惊吓反射的前脉冲抑制减少。这种行为障碍与短期内前额叶皮层前边缘和下边缘区域神经网络数量的减少有关。此外，青少年暴露于 JWH-018 会在两个时间间隔内诱导雄性小鼠前额皮质中小胶质细胞和星形胶质细胞的激活。在暴露于 JWH-018 的雄性小鼠中，还发现前额皮质中 GAD67 和 CB2 大麻素受体表达的暂时性下降。这些数据表明，在青春期使用 JWH-018 进行治疗会导致与精神病样症状相关的长期神经生物学变化，这些变化与性别有关。青少年暴露于 JWH-018 会在两个时间间隔内诱导雄性小鼠前额皮质中小胶质细胞和星形胶质细胞的激活。在暴露于 JWH-018 的雄性小鼠中，还发现前额皮质中 GAD67 和 CB2 大麻素受体表达的暂时性下降。这些数据表明，在青春期使用 JWH-018 进行治疗会导致与精神病样症状相关的长期神经生物学变化，这些变化与性别有关。青少年暴露于 JWH-018 会在两个时间间隔内诱导雄性小鼠前额皮质中小胶质细胞和星形胶质细胞的激活。在暴露于 JWH-018 的雄性小鼠中，还发现前额皮质中 GAD67 和 CB2 大麻素受体表达的暂时性下降。这些数据表明，在青春期使用 JWH-018 进行治疗会导致与精神病样症状相关的长期神经生物学变化，这些变化与性别有关。