Milanés M V, Laorden M L, Chapleur-Château M, Burlet A
Department of Physiology and Pharmacology, University School of Medicine, Murcia, Spain.
Naunyn Schmiedebergs Arch Pharmacol. 1997 Nov;356(5):603-10. doi: 10.1007/pl00005096.
The changes in the content of corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) in discrete brain nuclei during chronic opioids administration have not been well established. We evaluated the effects of acute and chronic morphine administration on the content of CRF and AVP in different hypothalamic and extrahypothalamic (bed nucleus of the stria terminalis, BNST) nuclei in rats. Concomitantly, changes in hypothalamic noradrenaline (NA) turnover [estimated by the 3-methoxy-4-hydroxyphenylethyleneglycol MHPG/NA ratio] and in plasma corticosterone release (as a marker of the activity of the hypothalamus-pituitary-adrenal axis) were determined. Male rats were implanted with placebo (naïve) or morphine (tolerant) pellets for 7 days. On day 8, groups of rats received an acute injection of either saline i.p. or morphine (30 mg/kg i.p.) and were sacrificed 30 min later. Acute morphine injection to naïve rats increased both the release of corticosterone and the hypothalamic NA turnover. CRF and AVP showed no modifications in the paraventricular nucleus (PVN) or in the median eminence (ME). CRF content decreased in the ventromedian nucleus (VMN) and increased in the BNST, but did not change in the arcuate nucleus (AN). AVP was elevated in the supraoptic nucleus (SON) but not changed in the suprachiasmatic nucleus (SCN). In chronic morphine-treated rats, there was a pronounced decrease in the NA turnover and in the release of corticosterone, which indicates that tolerance develops to the acute effects of morphine. Correspondingly, CRF and AVP were enhanced in the PVN and decreased in the ME, when compared with naïve rats injected with morphine. CRF content was decreased in the AN and in the BNST, but increased in the VMN. The AVP content was decreased in the SON, and no modifications were seen in the SCN. The present study shows that, in addition to the modifications in corticosterone secretion and in hypothalamic NA turnover, chronic morphine administration produces a complex response in the CRF and AVP systems. These modifications might contribute to the behavioral, emotional and neuroendocrine alterations produced during opioid tolerance.
长期给予阿片类药物期间，离散脑核中促肾上腺皮质激素释放因子（CRF）和精氨酸加压素（AVP）含量的变化尚未完全明确。我们评估了急性和慢性给予吗啡对大鼠不同下丘脑和下丘脑外（终纹床核，BNST）核团中CRF和AVP含量的影响。同时，测定了下丘脑去甲肾上腺素（NA）周转率的变化[通过3-甲氧基-4-羟基苯乙二醇（MHPG）/NA比值估算]以及血浆皮质酮释放量的变化（作为下丘脑-垂体-肾上腺轴活性的标志物）。雄性大鼠植入安慰剂（未处理）或吗啡（耐受）丸剂7天。在第8天，给大鼠组腹腔注射生理盐水或吗啡（30mg/kg腹腔注射），30分钟后处死。对未处理的大鼠急性注射吗啡增加了皮质酮的释放以及下丘脑NA周转率。CRF和AVP在室旁核（PVN）或正中隆起（ME）中未显示出变化。CRF含量在腹内侧核（VMN）中降低，在BNST中升高，但在弓状核（AN）中未改变。AVP在视上核（SON）中升高，但在视交叉上核（SCN）中未改变。在慢性吗啡处理的大鼠中，NA周转率和皮质酮释放量显著降低，这表明对吗啡的急性作用产生了耐受性。相应地，与注射吗啡的未处理大鼠相比，PVN中CRF和AVP增强，ME中降低。CRF含量在AN和BNST中降低，但在VMN中升高。AVP含量在SON中降低，SCN中未见变化。本研究表明，除了皮质酮分泌和下丘脑NA周转率的改变外，长期给予吗啡会在CRF和AVP系统中产生复杂的反应。这些改变可能导致阿片类药物耐受期间出现的行为、情绪和神经内分泌改变。
