近年来,D9-四氢大麻酚(THC)或含大麻的食品的消费量有所增加;然而,这种消耗的行为和神经回路效应仍然未知,特别是在摄入较高剂量导致大麻中毒的情况下。我们检查了急性大剂量食用大麻(AHDECC)的神经和行为影响。Sprague-Dawley大鼠(6只雄性,7名女性)在前额叶皮层(PFC)植入电极,背侧海马(dHipp),扣带皮质(Cg),和伏隔核(NAc)。为大鼠提供了10分钟的Nutella(6g/kg)和含THC的大麻油(20mg/kg)的混合物,在此期间,他们自愿食用所有提供的花生酱和THC混合物。暴露后2、4、8和24小时检查了大麻四分体和神经振荡。在另一群人中(16名男性,15名女性),我们研究了AHDECC对学习和前脉冲抑制的影响,以及血清和脑THC和11-羟基-THC浓度。AHDECC导致24小时以上雌性大鼠的大脑和血清THC和11-羟基THC水平较高。AHDECC还产生:1)Cg,dhipp,和NAc伽马功率抑制,雌性老鼠的抑制作用更大,以时间依赖的方式;2)运动不足,体温过低,和时间依赖性的抗伤害性感受;3)学习和脉冲前抑制障碍。此外,大多数神经活动和行为变化出现在摄入后2小时,这表明这段时间的干预措施可能会有效逆转/减少AHDECC的影响。意义声明大剂量食用大麻对行为和神经回路的影响知之甚少。我们发现急性大剂量食用大麻的影响,其中包括降低的伽马功率,体温过低,运动障碍,镇痛,学习和信息处理障碍,依赖于时间和性别。此外,这些效应在AHDECC后2小时开始,持续至少24小时,建议治疗应瞄准这个时间窗口才能有效。
The consumption of D9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (6 males, 7 females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Rats were provided access to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg) for 10 minutes, during which they voluntarily consumed all of the provided Nutella and THC mixture. Cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24-h after exposure. In another cohort (16 males, 15 females), we examined the effects of AHDECC on learning and prepulse inhibition, and serum and brain THC and 11-hydroxy-THC concentrations. AHDECC resulted in higher brain and serum THC and 11-hydroxy-THC levels in female rats over 24 h. AHDECC also produced: 1) Cg, dHipp, and NAc gamma power suppression, with the suppression being greater in female rats, in a time-dependent manner; 2) hypolocomotion, hypothermia, and anti-nociception in a time-dependent manner; and 3) learning and prepulse inhibition impairments. Additionally, most neural activity and behavior changes appear 2 h post-ingestion, suggesting that interventions around this time might be effective in reversing/reducing the effects of AHDECC. Significance Statement The effects of high-dose edible cannabis on behaviour and neural circuitry are poorly understood. We found that the effects of acute high-dose edible cannabis consumption, which include decreased gamma power, hypothermia, hypolocomotion, analgesia, and learning and information processing impairments, are time- and sex-dependent. Moreover, these effects begin 2 h after AHDECC and last for at least 24 h, suggesting that treatments should target this time window in order to be effective.