Opiate receptors modulate estrogen-induced cholecystokinin and tachykinin but not enkephalin messenger RNA levels in the limbic system and hypothalamus

• Published in: Neuroscience Vol. 80; no. 2; pp. 473 - 485
• Main Authors: Eckersell, C.B, Micevych, P.E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-1997; Elsevier
• Subjects: Animals; bed nucleus of the stria terminalis; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cholecystokinin - biosynthesis; Enkephalins - biosynthesis; Estrogens - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Hypothalamus - drug effects; Hypothalamus - metabolism; In Situ Hybridization; Limbic System - drug effects; Limbic System - metabolism; medial amygdala; medial preoptic nucleus; naltrexone; naltrindole; Narcotic Antagonists - pharmacology; Neurotransmitter Agents - biosynthesis; Ovariectomy; Rats; Receptors, Opioid - drug effects; Receptors, Opioid - physiology; RNA Probes; RNA, Messenger - biosynthesis; Tachykinins - biosynthesis; Vertebrates: nervous system and sense organs; β-funaltrexamine; BSTenc, encapsulated portion of the bed nucleus of the stria terminalis; naltrexone; MeApd, posterodorsal MeA; PAG, periaqueductal gray; EDTA, ethylenediaminetetra-acetate; MPNc, central portion of the medial preoptic nucleus; CCK, cholecystokinin; SP, substance P; β-funaltrexamine; medial preoptic nucleus; naltrindole; MeA, medial amygdala; VMH, ventromedial hypothalamic nucleus; medial amygdala; bed nucleus of the stria terminalis; PPT, preprotachykinin; Met-ENK, methionine enkephalin; PPE, preproenkephalin; β-FNA, β-funaltrexamine; bp, base pairs; Rat; Rodentia; Central nervous system; Enkephalin; Estrogen; Limbic system; Hypothalamus; Neuropeptide; Opiate receptor; Vertebrata; Mammalia; Cholecystokinin; Tachykinin; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(97)00072-9

Cholecystokinin, substance P and methionine enkephalin all regulate the display of reproductive behaviour. Their expression is exquisitely regulated by estrogen in the limbic–hypothalamic circuit, a circuit that regulates the display of estrogen-sensitive female reproductive behaviour. Relatively little is known, however, about the interaction of endogenous opioid peptides with cholecystokinin and substance P in the limbic–hypothalamic circuit. Opiates antagonize the release of cholecystokinin and substance P in the hypothalamus and periaqueductal gray and stimulate cholecystokinin messenger RNA levels in the amygdala. To determine the effect of endogenous opioid input on estrogen-induced cholecystokinin, enkephalin and substance P expression,
in situ hybridization histochemistry was used to examine estrogen-induced messenger RNA levels of these neuropeptides in specific nuclei of the limbic system and hypothalamus in the presence of opiate receptor antagonists. Estrogen treatment of ovariectomized rats significantly elevated cholecystokinin messenger RNA levels in the central portion of the medial preoptic nucleus, the encapsulated portion of the bed nucleus of the stria terminalis and the posterodorsal medial amygdala, as well as increased preproenkephalin and preprotachykinin messenger RNA levels in the ventromedial hypothalamic nucleus and the posterodorsal medial amygdala. The universal opiate receptor antagonist naltrexone and the
δ-opiate receptor antagonist naltrindole each potentiated the estrogen-induced increase and elevated cholecystokinin messenger RNA levels an additional 1.9- to 2.8-fold depending on the nucleus examined, but had no effect on the estrogen-induced expression of either preproenkephalin or preprotachykinin messenger RNA.
β-Funaltrexamine, a
μ-opiate receptor antagonist, had no effect on the medial preoptic or medial amygdaloid cholecystokinin messenger RNA levels or on the estrogen-induced expression of preproenkephalin messenger RNA but did cause a decrease in estrogen-induced cholecystokinin messenger RNA levels in the bed nucleus of the stria terminalis and a decrease in the preprotachykinin messenger RNA levels in the ventromedial hypothalamic nucleus.
These results indicate that endogenous opioids, acting on the
δ-opiate receptor within nuclei of the limbic–hypothalamic circuit, restrain the estrogen-induced increase of cholecystokinin messenger RNA expression. Activation of the
μ-opiate receptor, however, may facilitate cholecystokinin messenger RNA expression in the bed nucleus of the stria terminalis and preprotachykinin messenger RNA expression in the ventromedial hypothalamic nucleus. Thus, endogenous opioid peptides may act in a site- and receptor-specific manner to modulate estrogen-induced neuropeptide levels in the limbic system and hypothalamus.