Sumner B E, Coombes J E, Pumford K M, Russell J A
Department of Physiology, University Medical School, Edinburgh, U.K.
Neuroscience. 1990;37(3):635-45. doi: 10.1016/0306-4522(90)90095-l.
Morphine, given acutely, inhibits oxytocin secretion in adult female rats, but chronic intracerebroventricular infusion for five to six days induces tolerance and dependence in the mechanisms regulating oxytocin secretion. One explanation for tolerance could be that there is a loss of opioid receptors. To test this hypothesis cryostat sections of selected brain regions and the pituitary, from six control and six intracerebroventricular morphine-infused rats, were processed for quantitative in vitro receptor autoradiography. [3H]Etorphine or 3H-bremazocine were used as ligands, and DAGO, DPDPE and U50,488H as selective displacers from mu-, delta-, and kappa-receptors, respectively. Control incubations had naloxone determined specificity. The supraoptic nucleus (site of oxytocin-secreting magnocellular perikarya) contained both mu- and kappa-receptors in control rats (mean +/- S.E.M. binding of mu-selective [3H]etorphine was 91.8 +/- 25.4 fmol/mg of tissue, and of kappa-selective 3H-bremazocine was 130.4 +/- 25.6 fmol/mg). Chronic morphine treatment caused a 83.9% decrease in binding in mu-selective conditions (P less than 0.05), but no significant change in kappa-selective binding. In the median preoptic nucleus (which projects to the supraoptic nucleus) mean +/- S.E.M. binding of [3H]etorphine decreased by 77.0% (P less than 0.01) in chronic morphine-treated rats, from the control value of 76.2 +/- 9.8 fmol/mg of tissue. In the posterior pituitary gland (site of the terminals of the oxytocin-secreting magnocellular perikarya) binding with 3H-bremazocine in controls was over 90% lower than in the supraoptic nucleus. No changes followed chronic morphine treatment. Thus chronic morphine exposure reduces the numbers of available mu-receptors in the supraoptic nucleus, and of opioid receptors in the median preoptic nucleus, perhaps accounting for morphine-tolerance in relation to oxytocin secretion.
急性给予吗啡会抑制成年雌性大鼠的催产素分泌，但连续五到六天进行慢性脑室内注射会在调节催产素分泌的机制中诱导耐受性和依赖性。耐受性的一种解释可能是阿片受体的丧失。为了验证这一假设，对六只对照大鼠和六只经脑室内注射吗啡的大鼠的选定脑区和垂体进行冷冻切片处理，用于定量体外受体放射自显影。[3H]埃托啡或3H-布马佐辛用作配体，DAGO、DPDPE和U50,488H分别用作从μ-、δ-和κ-受体的选择性置换剂。对照孵育中使用纳洛酮确定特异性。视上核（分泌催产素的大细胞神经元胞体所在部位）在对照大鼠中同时含有μ-和κ-受体（μ-选择性[3H]埃托啡的平均±标准误结合量为91.8±25.4 fmol/mg组织，κ-选择性3H-布马佐辛的平均±标准误结合量为130.4±25.6 fmol/mg）。慢性吗啡治疗导致μ-选择性条件下的结合量减少83.9%（P<0.05），但κ-选择性结合无显著变化。在视前正中核（投射到视上核），慢性吗啡处理的大鼠中[3H]埃托啡的平均±标准误结合量从对照值76.2±9.8 fmol/mg组织下降了77.0%（P<0.01）。在垂体后叶（分泌催产素的大细胞神经元胞体终末所在部位），对照中与3H-布马佐辛结合量比视上核低90%以上。慢性吗啡治疗后无变化。因此，慢性吗啡暴露减少了视上核中可用μ-受体的数量以及视前正中核中阿片受体的数量，这可能是与催产素分泌相关的吗啡耐受性的原因。
