Landfield P W, Cadwallader L B, Vinsant S
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
Brain Res. 1988 Mar 8;443(1-2):47-62. doi: 10.1016/0006-8993(88)91597-1.
Although cannabinoids exert strong effects on brain function, there have been no extensive analyses of the long-term effects of cannabinoids on mammalian brain structure. Consequently, we conducted quantitative light and electron microscopic studies on the brains of rats treated chronically with delta 9-tetrahydrocannabinol (THC) (5 X weekly for 8 months--approximately 30% of the life-span). In these studies, we found significant THC-induced changes in hippocampal structure: specifically, THC-treated animals exhibited decreased neuronal density and increased glial cell reactivity (i.e. an increase of cytoplasmic inclusions). In addition, we confirmed prior reports of THC-induced increases in adrenal-pituitary activity, since both adrenocorticotropic hormone (ACTH) and corticosterone were elevated substantially during an acute stress. However, the animals appeared to be only minimally affected behaviorally by the doses used (highest dose: 8 mg/kg) and no effects of THC were observed on several ultrastructural variables, including synaptic density. The observed hippocampal morphometric effects of chronic THC are similar to apparent glucocorticoid-dependent changes that previously have been found to develop in rat hippocampus during normal aging. Given that cannabinoids and steroids are similar in chemical structure in several respects, therefore, the present results seem to raise the possibility that chronic THC exposure may alter hippocampal anatomical structure by interactions with, or mimicry of, adrenal steroid activity.
尽管大麻素对脑功能有显著影响，但尚未对大麻素对哺乳动物脑结构的长期影响进行广泛分析。因此，我们对长期接受δ9 - 四氢大麻酚（THC）治疗的大鼠大脑进行了定量光学和电子显微镜研究（每周5次，持续8个月——约占其寿命的30%）。在这些研究中，我们发现THC显著改变了海马结构：具体而言，接受THC治疗的动物神经元密度降低，胶质细胞反应性增加（即细胞质内含物增加）。此外，我们证实了之前关于THC导致肾上腺 - 垂体活动增加的报道，因为在急性应激期间促肾上腺皮质激素（ACTH）和皮质酮均大幅升高。然而，所用剂量（最高剂量：8 mg/kg）对动物行为的影响似乎微乎其微，并且未观察到THC对包括突触密度在内的几个超微结构变量有影响。慢性THC对海马形态测量的影响与之前在正常衰老过程中大鼠海马中发现的明显的糖皮质激素依赖性变化相似。鉴于大麻素和类固醇在化学结构的几个方面相似，因此，目前的结果似乎增加了长期接触THC可能通过与肾上腺类固醇活性相互作用或模拟肾上腺类固醇活性来改变海马解剖结构的可能性。
