Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects.
Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects.
复制标题
DOI：
10.1016/j.euroneuro.2008.06.009
复制
发表时间：
2008-11
影响因子：
5.6
通讯作者：
Hurd, Y. L.
中科院分区：
文献类型：
--
作者：
Ellgren, M.;Artmann, A.;Tkalych, O.;Gupta, A.;Hansen, H. S.;Hansen, S. H.;Devi, L. A.;Hurd, Y. L.
青春期是大脑活跃发育的关键阶段，其特点通常是开始使用大麻。有关青少年大脑的内源性大麻素系统以及似乎对大麻暴露敏感的相关神经递质的信息有限。我们最近观察到，在青春期预先暴露于Δ-9-四氢大麻酚(THC)的成年大鼠自我注射更高剂量的海洛因，并选择性地损害伏隔核内的脑啡肽阿片系统，这与奖赏相关行为有关。为了探索与青春期THC暴露相关的大麻素和阿片类神经系统的个体发育，在间歇性THC范式(1.5 mg/kg ip.每隔三天)，从出生后28天到49天。分别于注射PND 29(青春期早期)、PND 38(青春期中期)和PND 50(青春期晚期)后24小时检查大鼠脑内内源性大麻素(Anandide和2-花生四烯酸甘油)、甲硫氨酸脑啡肽、大麻素CB1受体和µ阿片受体(µOR)在NAc、尾壳核和前额叶皮质(PFC)的表达。在所研究的标记物中，内源性大麻素水平在整个青春期变化最剧烈，并且是PFC和NAC特有的。THC逆转了NAC(阳性)和PFC(阴性)中ANANDAME和2-花生四烯基甘油浓度之间的正常相关性。THC的其他显著作用仅限于NAC增加的ANANDAME、减少甲硫氨酸脑啡肽和减少uORs。这些发现强调了青春期中皮质边缘内源性大麻素系统的动态性质，以及青少年大麻暴露造成的选择性中皮质边缘障碍。
Adolescence is a critical phase of active brain development often characterized by the initiation of marijuana (Cannabis sativa) use. Limited information is known regarding the endogenous cannabinoid system of the adolescent brain as well as related neurotransmitters that appear sensitive to cannabis exposure. We recently observed that adult rats pre-exposed to Δ-9-tetrahydrocannabinol (THC) during adolescence self-administered higher amounts of heroin and had selective impairments of the enkephalin opioid system within the nucleus accumbens (NAc) implicated in reward-related behavior. To explore the ontogeny of the cannabinoid and opioid neuronal systems in association with adolescence THC exposure, rats were examined at different adolescent stages during an intermittent THC paradigm (1.5 mg/kg i.p. every third day) from postnatal days (PNDs) 28–49. Rat brains were examined 24 hours after injection at PND 29 (early adolescence), PND 38 (mid adolescence) and PND 50 (late adolescence) and analyzed for endocannabinoids (anandamide and 2-arachidonoylglycerol), Met-enkephalin, cannabinoid CB1 receptors and µ opioid receptors (µOR) in the NAc, caudate-putamen and prefrontal cortex (PFC). Of the markers studied, the endocannabinoid levels had the most robust alterations throughout adolescence and were specific to the PFC and NAc. Normal correlations between anandamide and 2-arachidonoylglycerol concentrations in the NAc (positive) and PFC (negative) were reversed by THC. Other significant THC-induced effects were confined to the NAc — increased anandamide, decreased Met-enkephalin and decreased µORs. These findings emphasize the dynamic nature of the mesocorticolimbic endocannabinoid system during adolescence and the selective mesocorticolimbic disturbance as a consequence of adolescent cannabis exposure.
登录
查看更多内容
DOI：
10.1073/pnas.0509494102
发表时间：
2005-12-27
影响因子：
11.1
作者：
Berghuis, P;Dobszay, MB;Harkany, T
通讯作者：
Harkany, T
影响因子：
2.9
作者：
González, S;Cascio, MG;Ramos, JA
通讯作者：
Ramos, JA
影响因子：
5.3
作者：
Caille, Stephanie;Alvarez-Jaimes, Lily;Parsons, Loren H.
通讯作者：
Parsons, Loren H.
影响因子：
8.2
作者：
Andersen, SL
通讯作者：
Andersen, SL
影响因子：
3.4
作者：
Bequet, Frederic;Uzabiaga, Francoise;Le Fur, Gerard
通讯作者：
Le Fur, Gerard