Corchero J, Fuentes J A, Manzanares J
Departamento de Farmacologia, Facultad de Farmacia, Instituto Pluridisciplinar, Universidad Complutense, Madrid, Spain.
Life Sci. 1999;64(11):905-11. doi: 10.1016/s0024-3205(99)00016-8.
The purpose of the present study was to explore the molecular mechanisms by which the cannabinoid system may interact with the hypothalamic-pituitary adrenal axis and the proopiomelanocortin opioid system. To this aim and by using in situ hybridization histochemistry, the effects of chronic (18 days) administration with the synthetic cannabinoid receptor agonist [(-)-cis-3-[2-hydroxy-4-(1,1,-dimethylheptyl)-phenyl]-trans-4(-3-h ydroxypropyl)cyclohexanol)], CP-55,940 (1 mg/kg/day; i.p.) on corticotropin releasing factor and proopiomelanocortin gene expression were examined in the paraventricular and arcuate nuclei of the hypothalamus and anterior and intermediate lobes of the pituitary gland in the rat. Chronic administration with CP-55,940 increased corticotropin releasing factor mRNA levels (41%) in the paraventricular nucleus and proopiomelanocortin mRNA levels in the arcuate nucleus (25%) and anterior lobe of the pituitary (30%), but decreased (28%) of proopiomelanocortin transcript amounts in the intermediate lobe of the pituitary. These results revealed that chronic cannabinoid administration enhances corticotropin releasing factor and proopiomelanocortin gene expression in the hypothalamus and anterior pituitary, a process that may be considered as part of a molecular integrative response to the stress associated to cannabinoid drug abuse.
本研究的目的是探讨大麻素系统可能与下丘脑-垂体-肾上腺轴以及阿片促黑激素原阿片系统相互作用的分子机制。为了实现这一目标并使用原位杂交组织化学方法，研究了在大鼠下丘脑的室旁核和弓状核以及垂体前叶和中叶中，慢性（18天）给予合成大麻素受体激动剂[(-)-顺式-3-[2-羟基-4-(1,1-二甲基庚基)-苯基]-反式-4(-3-羟丙基)环己醇]，即CP-55,940（1毫克/千克/天；腹腔注射）对促肾上腺皮质激素释放因子和阿片促黑激素原基因表达的影响。慢性给予CP-55,940可使室旁核中的促肾上腺皮质激素释放因子mRNA水平增加（41%），弓状核中的阿片促黑激素原mRNA水平增加（25%）以及垂体前叶中的阿片促黑激素原mRNA水平增加（30%），但垂体中叶中的阿片促黑激素原转录本量减少（28%）。这些结果表明，慢性给予大麻素可增强下丘脑和垂体前叶中促肾上腺皮质激素释放因子和阿片促黑激素原的基因表达，这一过程可被视为对与大麻素药物滥用相关的应激反应进行分子整合的一部分。
