Fetal cannabidiol (CBD) exposure alters thermal pain sensitivity, problem-solving, and prefrontal cortex excitability.
Fetal cannabidiol (CBD) exposure alters thermal pain sensitivity, problem-solving, and prefrontal cortex excitability.
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DOI：
10.1038/s41380-023-02130-y
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发表时间：
2023-08
影响因子：
11
通讯作者：
Bates, Emily Anne
中科院分区：
文献类型：
--
作者：
Swenson, Karli S.;Gomez Wulschner, Luis E.;Hoelscher, Victoria M.;Folts, Lillian;Korth, Kamryn M.;Oh, Won Chan;Bates, Emily Anne
每年都有成千上万的人因怀孕而恶心。恶心可以用大麻二酚（CBD）来缓解，大麻二酚是大麻的主要成分，可以广泛获得。然而，胎儿暴露于CBD如何影响胚胎发育和产后结局尚不清楚。CBD结合并激活在胎儿大脑中表达的受体，这些受体对大脑发育很重要，包括5 -羟色胺受体（5HT1A）、电压门控钾（Kv）7受体和瞬时电位香草样蛋白1受体（TRPV1）。这些受体的过度激活会破坏神经发育。在这里，我们验证了胎儿暴露在小鼠体内会改变后代神经发育和产后行为的假设。从胚胎第5天到出生，我们给怀孕小鼠注射葵花籽油或单独的葵花籽油中50 mg/kg的CBD。我们发现胎儿暴露于CBD会通过TRPV1使成年雄性后代对热痛敏感。我们发现胎儿暴露于CBD会减少雌性暴露于CBD的后代解决问题的行为。研究表明，胎儿暴露于CBD会增加雌性后代2/3层前额叶皮质（PFC）锥体神经元引发动作电位所需的最小电流，并减少动作电位的数量。胎儿暴露于CBD会降低谷氨酸释放诱发的兴奋性突触后电流的振幅，这与暴露于CBD的女性解决问题行为缺陷一致。综上所述，这些数据表明胎儿暴露于CBD会以一种性别特异性的方式破坏神经发育和产后行为。
Thousands of people suffer from nausea with pregnancy each year. Nausea can be alleviated with cannabidiol (CBD), a primary component of cannabis that is widely available. However, it is unknown how fetal CBD exposure affects embryonic development and postnatal outcomes. CBD binds and activates receptors that are expressed in the fetal brain and are important for brain development, including serotonin receptors (5HT1A), voltage-gated potassium (Kv)7 receptors, and the transient potential vanilloid 1 receptor (TRPV1). Excessive activation of each of these receptors can disrupt neurodevelopment. Here, we test the hypothesis that fetal CBD exposure in mice alters offspring neurodevelopment and postnatal behavior. We administered 50 mg/kg CBD in sunflower oil or sunflower oil alone to pregnant mice from embryonic day 5 through birth. We show that fetal CBD exposure sensitizes adult male offspring to thermal pain through TRPV1. We show that fetal CBD exposure decreases problem-solving behaviors in female CBD-exposed offspring. We demonstrate that fetal CBD exposure increases the minimum current required to elicit action potentials and decreases the number of action potentials in female offspring layer 2/3 prefrontal cortex (PFC) pyramidal neurons. Fetal CBD exposure reduces the amplitude of glutamate uncaging-evoked excitatory post-synaptic currents, consistent with CBD-exposed female problem-solving behavior deficits. Combined, these data show that fetal CBD exposure disrupts neurodevelopment and postnatal behavior in a sex specific manner.
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影响因子：
16.6
作者：
Hurtado-Zavala JI;Ramachandran B;Ahmed S;Halder R;Bolleyer C;Awasthi A;Stahlberg MA;Wagener RJ;Anderson K;Drenan RM;Lester HA;Miwa JM;Staiger JF;Fischer A;Dean C
通讯作者：
Dean C
影响因子：
3
作者：
Albert PR;Vahid-Ansari F;Luckhart C
通讯作者：
Luckhart C
影响因子：
3.6
作者：
FELICIO, LS;NELSON, JF;FINCH, CE
通讯作者：
FINCH, CE
DOI：
10.1523/jneurosci.6451-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cavanaugh DJ;Chesler AT;Jackson AC;Sigal YM;Yamanaka H;Grant R;O'Donnell D;Nicoll RA;Shah NM;Julius D;Basbaum AI
通讯作者：
Basbaum AI
影响因子：
3.3
作者：
Bonnin, A.;Peng, W.;Levitt, P.
通讯作者：
Levitt, P.