Department of Pharmacology and Toxicology and Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, VA, USA.
Br J Pharmacol. 2010 Sep;161(1):103-12. doi: 10.1111/j.1476-5381.2010.00870.x.
Disruption of the substantial re-organization of the brain during adolescence may be induced by persistent abuse of marijuana. The aim of this study was to determine whether adolescent and adult rats exhibit differential adaptation of brain cannabinoid (CB(1)) receptors after repeated exposure to Delta(9)-tetrahydrocannabinol (THC).
Rats of both ages and sexes were dosed with 10 mg kg(-1) THC or vehicle twice daily for 9.5 days. Subsequently, CB(1) receptor function and density were assessed.
In all brain regions, THC treatment produced desensitization and down-regulation of CB(1) receptors. While the magnitude of down-regulation did not differ across groups, greater desensitization was evident in the brains of THC-treated female adolescent rats for most regions. Adolescent females showed greater desensitization than adult females in the prefrontal cortex, hippocampus, periaqueductal gray (PAG) and ventral midbrain. In contrast, adolescent males exhibited less desensitization in the prefrontal cortex, hippocampus and PAG, an effect opposite to that seen in females. With the exception of the PAG, sex differences were seen only in adolescents, with greater desensitization in the prefrontal cortex, striatum, hippocampus, PAG, and ventral midbrain of females.
These results suggest that the brains of adolescent females may be particularly vulnerable to disruption of CB(1) receptor signalling by marijuana abuse. Alternatively, increased desensitization may reflect protective adaptation. Given the extensive re-organization of the brain during adolescence, this disruption has potential long-term consequences for maturation of the endocannabinoid system.
在青春期，大脑的实质性重组可能会因大麻的持续滥用而受到破坏。本研究的目的是确定青春期和成年大鼠在反复暴露于Δ9-四氢大麻酚（THC）后，大脑大麻素（CB1）受体是否表现出不同的适应性。
青春期和成年的雌雄大鼠每天两次接受 10mg/kg THC 或载体处理 9.5 天。随后评估 CB1 受体功能和密度。
在所有脑区，THC 处理均导致 CB1 受体脱敏和下调。虽然下调的幅度在各组之间没有差异，但在大多数区域，接受 THC 处理的青春期雌性大鼠的脱敏作用更为明显。与成年雌性大鼠相比，青春期雌性大鼠的前额叶皮层、海马体、导水管周围灰质（PAG）和腹侧中脑的脱敏作用更大。相比之下，青春期雄性大鼠在前额叶皮层、海马体和 PAG 中的脱敏作用较小，这种作用与雌性大鼠相反。除 PAG 外，仅在青春期大鼠中观察到性别差异，雌性大鼠的前额叶皮层、纹状体、海马体、PAG 和腹侧中脑的脱敏作用更大。
这些结果表明，青春期雌性大鼠的大脑可能特别容易受到大麻滥用对 CB1 受体信号的破坏。或者，增加的脱敏作用可能反映了保护性适应。鉴于青春期大脑的广泛重组，这种破坏可能对内源性大麻素系统的成熟产生潜在的长期影响。
