Opioid and cannabinoid receptor-mediated regulation of the increase in adrenocorticotropin hormone and corticosterone plasma concentrations induced by central administration of Δ9-tetrahydrocannabinol in rats
Opioid and cannabinoid receptor-mediated regulation of the increase in adrenocorticotropin hormone and corticosterone plasma concentrations induced by central administration of Δ9-tetrahydrocannabinol in rats
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DOI：
10.1016/s0006-8993(99)01756-4
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发表时间：
1999-08-21
期刊：
影响因子：
2.9
通讯作者：
Fuentes, JA
中科院分区：
文献类型：
--
作者：
Manzanares, J;Corchero, J;Fuentes, JA
本研究旨在探讨大麻样物质和阿片类物质对中央三角洲(9)-四氢大麻酚(Delta(9)-THC)对雄性大鼠下丘脑-垂体-肾上腺(HPA)轴活动的调节作用。脑室内(i.c.v.)Delta(9)-THC(25、50、100 mU g/只)可显著增加血浆促肾上腺皮质激素(ACTH)和皮质酮的浓度。时程效应研究表明，两种激素的分泌均在Delta(9)-THC静注后60min达到高峰。给药(50微克/只大鼠)，逐渐下降，并在480分钟时恢复到基线水平。肌肉注射特异性大麻素受体拮抗剂SR-141716A(3mUg/只)可显著减弱Delta(9)-THC(50mUg/只)引起的两种激素分泌的增加。然而，较高剂量(12.5和50mUg/只)的这种化合物增加了ACTH和皮下皮质酮的血浆浓度。注射阿片受体拮抗剂纳洛酮(0.3 mg/kg)对Delta(9)-THC(50 mU/g/只)引起的上述两种激素分泌的增加无明显作用，但可显著抑制Delta(9)-THC引起的上述两种激素分泌的增加。综上所述，这些结果表明阿片受体和大麻素受体参与了Delta(9)-THC诱导的HPA轴的激活。此外，给予比阻断这种激活所需剂量更高剂量的SR-141716A后，ACTH和皮质酮的分泌增加，这表明内源性大麻素正在紧张性地抑制这两种激素的释放，或者这种激动剂样活动可能是这种化合物未经大麻素受体介导的未知作用的一部分。(C)1999 Elsevier Science B.V.保留所有权利。
The purpose of this study was to investigate the cannabinoid and opioid mediated regulation on the effects of central Delta(9)-tetrahydrocannabinol (Delta(9)-THC) administration on hypothalamus-pituitary-adrenal (HPA) axis activity in the male rat. Intracerebroventricular (i.c.v.) administration of Delta(9)-THC (25, 50, 100 mu g/rat) markedly increased plasma adrenocorticotropin hormone (ACTH) and corticosterone concentrations. Time course effect studies revealed that both hormones secretion peaked at 60 min after Delta(9)-THC i.c.v. administration (50 mu g/rat), decreased gradually and returned to baseline levels by 480 min. The i.c.v, administration of the specific cannabinoid receptor antagonist SR-141716A (3 mu g/rat) significantly attenuated the increase of both hormones secretion induced by Delta(9)-THC (50 mu g/rat). Nevertheless, higher doses (12.5 and 50 mu g/rat) of this compound increased both ACTH and corticosterone plasma concentrations, Subcutaneous (s.c.) administration with the opiate receptor antagonist naloxone (0.3 mg/kg) was without effect but significantly diminished the increase of both hormones secretion induced by Delta(9)-THC (50 mu g/rat). Taken together, these results indicate that opiate and cannabinoid receptors are involved in the activation of the HPA axis induced by Delta(9)-THC. Furthermore, the increase of ACTH and corticosterone secretion after the administration of higher doses of SR-141716A than those required to block such activation, suggests that endogenous cannabinoids are tonically inhibiting the release of both hormones or that this agonist-like activity may be part of an uncharacterized action of this compound not mediated by cannabinoid receptors. (C) 1999 Elsevier Science B.V. All rights reserved.