Hattori Y, Katafuchi T, Koizumi K
Department of Physiology, State University of New York, Brooklyn 11203.
Brain Res. 1991 Jan 11;538(2):283-8. doi: 10.1016/0006-8993(91)90441-w.
In previous studies we found that in the extremely polydipsic special strain of mice, STR/N, spontaneous drinking was greatly attenuated by injection of the opioid antagonists given intracerebroventricularly as well as subcutaneously. Therefore, we investigated, using hypothalamic slice preparations, responses of neurons in the anteroventral third ventricle region (AV3V) of the STR/N and its control, Swiss/Webster (S/W) mice to morphine and opiate peptides. An application of morphine at 10(-6) M to the circulating medium inhibited activities of 44% of AV3V neurons (45 of 102) in the STR/N, and 59% (76/129) in the S/W, demonstrating that morphine affected a smaller proportion of neurons of the polydipsic mice than that of controls. Opioid agonists for 3 receptor types, mu, delta and kappa, at 10(-6) to 10(-5) M inhibited AV3V neurons in both the STR/N and S/W mice, but to a different degree. No cell of either strain was excited by morphine or any of the opioids. The mu-receptor agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAGO), was the most potent inhibitor of AV3V neurons; in the STR/N 53% (25/47), and in the S/W 77% (34/44) were inhibited. The kappa-agonist, dynorphin A-(1-13) (DYN), inhibited fewer cells in the STR/N (9%, 4/47), compared with the S/W (36%, 16/44). Only a few cells responded to the delta-agonist, [D-Pen2,5]enkephalin (DPDPE), in both strains. The inhibitory actions of the opiates were reversibly blocked by naloxone, and persisted under synaptic blockade. The threshold concentration of morphine or DAGO for inhibition of AV3V neurons was higher in the STR/N (approximately 10(-8) M for both morphine and DAGO) than in S/W mice (approximately 10(-9) M for morphine and less than 10(-9) M for DAGO). Although the AV3V also contains angiotensin II-sensitive neurons, they were not affected by morphine (10(-6) M). Similarly neurons inhibited by morphine were not excited by angiotensin II (10(-7) M); some neurons were unresponsive to both chemicals. We conclude that morphine and opiate peptides directly inhibit the AV3V neurons of both the STR/N and S/W strains of mice and the sensitivity of these neurons to the opiates is lower in the polydipsic inbred mice compared to their controls. The results, together with our behavioral studies, suggest involvement of the central opioid system in the polydipsia of the STR/N mice.
在先前的研究中，我们发现，在极度多饮的STR/N特殊品系小鼠中，脑室内及皮下注射阿片类拮抗剂可显著减弱其自发饮水行为。因此，我们利用下丘脑脑片标本，研究了STR/N小鼠及其对照瑞士 Webster（S/W）小鼠的第三脑室前腹侧区（AV3V）神经元对吗啡和阿片肽的反应。向灌流液中加入10⁻⁶ M吗啡，可抑制STR/N小鼠中44%（102个中的45个）的AV3V神经元活动，以及S/W小鼠中59%（129个中的76个）的神经元活动，表明吗啡对多饮小鼠神经元的影响比例小于对照小鼠。三种阿片受体类型（μ、δ和κ）的阿片激动剂，浓度为10⁻⁶至10⁻⁵ M时，均可抑制STR/N和S/W小鼠的AV3V神经元，但程度不同。两种品系的小鼠中均没有细胞被吗啡或任何一种阿片类物质兴奋。μ受体激动剂[D-Ala²，N-Me-Phe⁴，Gly⁵-ol]-脑啡肽（DAGO）是AV3V神经元最有效的抑制剂；在STR/N小鼠中，53%（47个中的25个）的神经元被抑制，在S/W小鼠中，77%（44个中的34个）的神经元被抑制。κ激动剂强啡肽A-（1-13）（DYN）在STR/N小鼠中抑制的细胞数量（9%，47个中的4个）少于S/W小鼠（36%，44个中的16个）。两种品系中只有少数细胞对δ激动剂[D-Pen²，⁵]脑啡肽（DPDPE）有反应。阿片类物质的抑制作用可被纳洛酮可逆性阻断，并在突触阻断下持续存在。抑制STR/N小鼠AV3V神经元的吗啡或DAGO的阈值浓度（吗啡和DAGO均约为10⁻⁸ M）高于S/W小鼠（吗啡约为10⁻⁹ M，DAGO小于10⁻⁹ M）。虽然AV3V中也含有对血管紧张素II敏感的神经元，但它们不受吗啡（10⁻⁶ M）影响。同样，被吗啡抑制的神经元也不会被血管紧张素II（10⁻⁷ M）兴奋；一些神经元对这两种化学物质均无反应。我们得出结论，吗啡和阿片肽可直接抑制STR/N和S/W品系小鼠的AV3V神经元，与对照小鼠相比，多饮近交系小鼠中这些神经元对阿片类物质的敏感性较低。这些结果与我们的行为学研究结果一起表明，中枢阿片系统参与了STR/N小鼠的多饮行为。
