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Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2018-07-10 , DOI: 10.1038/s41401-018-0073-z
Alex Perchuk 1 , Sonya M Bierbower 1 , Ana Canseco-Alba 1 , Zoila Mora 1 , Lauren Tyrell 1 , Neal Joshi 1 , Norman Schanz 1 , Georgianna G Gould 2 , Emmanuel S Onaivi 1
Affiliation  

Despite the apparent abundance of ligand-gated transient receptor potential vanilloid type 1 (TRPV1) and possible cross talk between the endocannabinoid and endovanilloid systems in the central nervous system (CNS), it is unclear what role TRPV1 receptor activation in CNS plays in neurobehavioral development. We previously reported that capsaicin or WIN55212-2 induces risk aversion in the plus-maze test, which was dependent on the gender and mouse strain used. In this study, pregnant BALBc mice were administered capsaicin (1.0 or 4.0 mg/kg, i.p.) during the second week of gestation. Developmental effects of prenatal exposure to capsaicin were assessed in neonates, and behavioral effects were assessed in adult offspring. Gender- and dose-specific variations in ultrasonic vocalizations, weight gain, righting reflex, and general activity of the pups were observed. Prenatal exposure to capsaicin altered plus-maze performance, especially with further exogenous capsaicin challenge. Furthermore, dose- and gender-specific effects were evident in the conditioned place preference/aversion paradigm following conditioning with capsaicin in adult animals. The capsaicin-induced aversion in the plus-maze test was enhanced by WIN55212-2 and blocked by pretreatment with vanilloid antagonist capsazepine or the CB1 receptor antagonist rimonabant, demonstrating an interaction between the endocannabinoid and endovanilloid systems in CNS. Taken together, the interaction between the endocannabinoid and endovanilloid signaling systems can be exploited for therapeutic applications in health and disease.

中文翻译:

辣椒素在产前激活内源性大麻素受体后对新生和成年小鼠的发育和行为影响。

尽管配体门控瞬时受体电位 1 型 (TRPV1) 明显丰富,并且中枢神经系统 (CNS) 中的内源性大麻素和内源性类香草素系统之间可能存在串扰,但尚不清楚 CNS 中 TRPV1 受体激活在神经行为发育中的作用. 我们之前报道过辣椒素或 WIN55212-2 在加号迷宫测试中诱导风险厌恶,这取决于所使用的性别和小鼠品系。在这项研究中,怀孕的 BALBc 小鼠在妊娠的第二周被给予辣椒素(1.0 或 4.0 mg/kg,ip)。在新生儿中评估产前暴露于辣椒素的发育影响,并在成年后代中评估行为影响。超声波发声、体重增加、翻正反射的性别和剂量特异性变化,观察幼崽的一般活动。产前接触辣椒素会改变加迷宫的表现,尤其是在进一步外源性辣椒素挑战的情况下。此外,在成年动物用辣椒素调理后,在条件性位置偏好/厌恶范式中,剂量和性别特异性效应很明显。WIN55212-2 增强了加迷宫试验中辣椒素诱导的厌恶,并通过用香草素拮抗剂卡西平或 CB1 受体拮抗剂利莫那班预处理阻断,证明了 CNS 中内源性大麻素和内源性香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。特别是在进一步外源性辣椒素挑战的情况下。此外,在成年动物用辣椒素调理后,在条件性位置偏好/厌恶范式中,剂量和性别特异性效应很明显。WIN55212-2 增强了加迷宫试验中辣椒素诱导的厌恶,并通过用香草素拮抗剂卡西平或 CB1 受体拮抗剂利莫那班预处理阻断,证明了 CNS 中内源性大麻素和内源性香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。特别是在进一步外源性辣椒素挑战的情况下。此外,在成年动物用辣椒素调理后,在条件性位置偏好/厌恶范式中,剂量和性别特异性效应很明显。WIN55212-2 增强了加迷宫试验中辣椒素诱导的厌恶,并通过用香草素拮抗剂卡西平或 CB1 受体拮抗剂利莫那班预处理阻断,证明了 CNS 中内源性大麻素和内源性香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。在成年动物用辣椒素调理后,在条件性位置偏好/厌恶范式中,剂量和性别特异性效应很明显。WIN55212-2 增强了加迷宫试验中辣椒素诱导的厌恶,并通过用香草素拮抗剂卡西平或 CB1 受体拮抗剂利莫那班预处理阻断,证明了 CNS 中内源性大麻素和内源性香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。在成年动物用辣椒素调理后,在条件性位置偏好/厌恶范式中,剂量和性别特异性效应很明显。WIN55212-2 增强了加迷宫试验中辣椒素诱导的厌恶,并通过用香草素拮抗剂卡西平或 CB1 受体拮抗剂利莫那班预处理阻断,证明了 CNS 中内源性大麻素和内源性香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。证明了 CNS 中内源性大麻素和内源性类香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。证明了 CNS 中内源性大麻素和内源性类香草素系统之间的相互作用。总之,内源性大麻素和内源性香草素信号系统之间的相互作用可用于健康和疾病的治疗应用。
更新日期:2018-07-12
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