- Email: [email protected]
Response of neuropeptide Y-induced feeding to μ-, δ- and κ-opioid receptor antagonists in the neonatal chick
Neuroscience Letters 373 (2005) 85–88
Response of neuropeptide Y-induced feeding to -, ␦- and -opioid receptor antagonists in the neonatal chick Koh-Ichi Dodo, Tomofumi Izumi, Hiroshi Ueda, Takashi Bungo∗ Laboratory of Animal Science, Department of Agrobiological Science, Faculty of Agriculture, Ehime University, Tarumi 3-5-7 Matsuyama, Ehime 790-8566, Japan Received 2 July 2004; received in revised form 13 August 2004; accepted 27 September 2004
Abstract It is known that opioid antagonists reduce the orexigenic effect of neropeptide Y (NPY) in mammals. We studied the effect of three opioid antagonists on NPY-induced feeding in male broiler chicks. -Funaltrexamine (-FNA), naloxonazine (NAL), ICI-174,864 (ICI) or nor-binaltorphimine (nor-BNI), antagonists of -, 1 -, ␦- or -receptors, and NPY were co-injected in chicks. Food intake was measured 30 min after treatment. Co-injection of -FNA or NAL was effective in reducing NPY-induced feeding, whereas ICI and nor-BNI had little effect on NPY-induced feeding. These data suggest that the -opioid receptor, especially the 1 -opioid has some relation to NPY-induced feeding, and implies that an endogenous ligand, such as -endorphin, participates in the orexigenic effect of NPY in neonatal chicks. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Feeding behavior; Neuropeptide Y (NPY); Opioid; Chick; -Receptor; ␦-Receptor; -Receptor
Research over the past several decades has examined the brain neurochemical systems that regulate food intake in mammalian species, and have identified a number of major central neurotransmitter circuits that appear to contribute to this behavior. Opiates and neuropeptide Y (NPY), the potent stimulators of feeding behavior in the rat [7,9], are found in brain areas known to be involved in the control of ingestive behavior [3]. Similar to mammalians, both peptides have been shown to exist in various regions of chick brain [4,13]. Then, it was reported that intracerebroventricular (ICV) injection of opioids or NPY increased food intake of the chick and chicken [15,18,19,22]. For the past decade, much evidence in mammals has been collected suggesting a functional link between NPY and -endorphin (-END), one of the endogenous opioids (e.g., [10]). However, no information about the relationship between them in avian species is available. The purpose of this study was to examine the effect of each opioid receptor antagonist on NPY-induced feeding in chicks.
∗
Corresponding author. Tel.: +81 89 946 9820; fax: +81 89 946 9820. E-mail address: [email protected] (T. Bungo).
0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.09.065
Day-old male broiler chicks (Cobb) were purchased from a local hatchery (Fresh Foods, Ehime, Japan). The birds were maintained in a room with 24-h lighting and at a temperature of 30 ◦ C. They were given free access to a commercial starter diet (Nihon Nosan Kogyo Co. Ltd., Yokohama, Japan) and water during the pre-experimental period. The chicks were maintained in accordance with the recommendations of the National Research Council [20]. They were distributed into experimental groups based on their body weight so that the average body weight was as uniform as possible for each treatment. The birds were reared individually in experimental cages and had ad libitum access to food up to the time of experiments. Birds (2 or 3 days old) fed ad libitum were given diet for 30 min immediately after treatment. Food intake was determined by measuring the reduction of diet from a preweighed feeder. The weight of feeders was measured using an electric digital balance of precision ±1 mg. NPY (porcine), naloxonazine dihydrochloride (NAL; a selective 1 -opioid receptor antagonist) and norbinaltorphimine dihydrochloride (nor-BNI; a selective opioid receptor antagonist) were purchased from Sigma (St. Louis, MO, USA), and -funaltrexamine hydrochloride (-
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K.-I. Dodo et al. / Neuroscience Letters 373 (2005) 85–88
FNA; a selective -opioid receptor antagonist) and ICI174,864 (ICI; a selective ␦-opioid receptor antagonist) were obtained from Tocris Cookson (Bristol, UK). The drugs were dissolved in a 0.1% Evans Blue solution, which was prepared in 0.85% saline. Saline containing Evans Blue was used as a control. The birds were ICV injected with the solutions (10 l) using a microsyringe according to the methods used by Davis et al. [8]. Each chick was injected once only with saline, NPY, each opioid receptor antagonist or antagonist co-injected with NPY. The doses of opioid antagonists applied here were decided according to the preliminary trials, in which these doses of antagonists did not elicit any abnormal behavior (such as depression) in ad libitum chicks. At the end of the experiments, birds were sacrificed by decapitation, after which the location of the injection site was confirmed. Data from the individuals that were not verified by the presence of Evans Blue dye in the lateral ventricle were deleted. The number of birds used for data analysis is shown in each figure. Data were analyzed by two-way ANOVA with respect to the effects of NPY and each opioid antagonist. A post hoc test was done using Fisher’s LSD test. Statistical significance was set at P < 0.05. Data were expressed as means ± S.E.M. The effect of ICV co-injection of -FNA (10 g) and NPY (1 g) on food intake in broiler chicks at 30 min after injection is shown in Fig. 1. Food intake of the NPY plus -FNA group was greater than that of the control group, but was lower than that of the NPY alone group. Significant NPY [F(l,29) = 158.14, P < 0.001] and -FNA [F(l,29) = 8.562, P < 0.01] effects were observed. A significant interaction between NPY and -FNA [F(l,29) = 8.663, P < 0.01] was also detected. The effect of -FNA on NPY-induced food intake was potent, reducing NPY-induced feeding by 35% in the 0–30-min feeding interval.
Fig. 1. Effects of -funaltrexamine (-FNA) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 8; -FNA, 8; NPY, 10; NPY + -FNA, 7.
Fig. 2. Effects of naloxonazine (NAL) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 10; NAL, 7; NPY, 9; NPY + NAL, 7.
Fig. 2 shows the effect of NAL (10 g) on NPY (1 g)-induced feeding in chicks. Significant NPY [F(1,29) = 103.00, P < 0.001] and NAL [F(1,29) = 10.762, P < 0.01] effects were observed. A significant interaction between NPY and NAL [F(1,29) = 7.665, P < 0.01] was also detected. Similar to -FNA the effect of NAL on NPYinduced food intake was potent, reducing NPY-induced feeding during the experimental period. The effect of ICV co-iniection of ICI (4 g) and NPY (1 g) on food intake in chicks is shown in Fig. 3. Food intake of the NPY alone group and the NPY plus ICI group were greater than that of the control group. Significant NPY
Fig. 3. Effects of ICI-174,864 (ICI) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 11; ICI, 8; NPY, 7; NPY + ICI, 8.
K.-I. Dodo et al. / Neuroscience Letters 373 (2005) 85–88
[F(l,30) = 42.614, P < 0.001] effect was found, but no significant ICI effect [F(l,30) = 0.302, P > 0.05] or interaction between treatments [F(l,30) = 1.488, P > 0.05]. Fig. 4 shows the effect of ICV co-injection of norBNI (2 g) and NPY (1 g) on food intake in chicks. Significant NPY [F(l,30) = 107.00, P < 0.001] and nor-BNI [F(l,30) = 5.289, P < 0.05] effects were observed. Food intake of the NPY plus nor-BNI group was greater than that of the control group, but was lower than that of the NPY alone group. However, no significant interaction [F(l,30) = 0.001, P > 0.05] was detected. These results suggest that NPY-induced feeding has a relationship with the opioidergic system through the -opioid receptor in chicks (Figs. 1 and 2). In particular, the system via the 1 -opioid receptor seemed to be important for the orexigenic effect of NPY in chicks. In mammals, it is known that the -opioid receptor is subdivided into two subtypes (1 and 2 -receptor) and equally sensitive ingestive response to -FNA (both 1 - and 2 -opioid receptors) and NAL (1 opioid receptor) suggest 1 -receptor mediation of that response [2]. Although there are no report about the roles of each heteroreceptor in chicks, it is also likely that the stimulation via 1 -opioid receptor might modulate feeding regulation in chicks. As for the relationship between NPY and endogenous opioids, it is reported that NPY-producing neurons are synaptically linked with -END-producing neurons in the arcuate nucleus of rats [10]. Additionally, similar to NPY, -END injected into the hypothalamus also increased feeding in rats (e.g., [16]). It is suggested that NPY may induce feeding directly on its own and also by stimulating -END in relevant sites of the brain [12]. In the case of chickens, McCormack and Denbow [18] demonstrated that -END likewise stimulates food intake in both meat- and layer-type chickens. Thus, although the morphological link between NPY and -END in the chicken hypothalamus has not been identified, it is
87
possible that -END participates in NPY-induced feeding in chicks. Although -END is an endogenous ligand for both and ␦-opioid receptors, ␦-opioid antagonist (ICI) did not attenuate NPY-induced food intake in chicks (Fig. 3). In the preliminary trial, we found that central administration of ICI (4 g) decreased deprivation-induced feeding 30 min after presentation of food by as much as 25% (unpublished data). These results suggest that deprivation-induced feeding, but not NPY-induced feeding, might interact with the opioidergic system through the ␦-opioid receptors in chicks. This result is in agreement with a previous report, which showed that but not ␦-opioid antagonist decreased NPY-induced feeding in rats [14]. The possible reason for the ineffective ␦-opioid antagonist on NPY-induced feeding could be attributed to a lack of ␦-opioid receptors in relevant sites. In the aforementioned brain site (the arcuate nucleus), morphological studies showed that the -opioid receptor was expressed [1,5,21], while the ␦-opioid receptor was not [17]. In a previous study, we found that food intake at 30 min was increased by ICV injection of -opioid receptor agonists (U-50488H and U-62066) in chicks [6]. On the other hand, the result in this study showed that -opioid antagonist (norBNI) did not attenuate NPY-induced food intake in chicks (Fig. 4). Similar to this result, GNTI (a newly synthesized antagonist selective for -opioid receptors) was ineffective in reducing the orexigenic effect of NPY in rats [11]. Accordingly, it is unlikely that an endogenous ligand for the -opioid receptor, such as dynorphin, might participate in NPY-induced feeding in both chicks and rats. Recently, Boswell [4] has revealed the existence of nutritionally sensitive neurons expressing NPY in the hypothalamic infundibular nucleus of birds that appear to be neuroanatomically equivalent to NPY neurons in the arcuate nucleus of the mammalian hypothalamus. Thus, it is likely that the linkage (NPY--END) in chicks may exist in the infundibular nucleus. Clearly, further work for neuroanatomical research is necessary in chickens. However, the results presented here suggest that the opioidergic system through the 1 -opioid receptor, especially the 1 -opioid, has a relationship with the orexigenic effect of NPY in chicks. Additionally, NPY may stimulate the release and/or synthesis of -END in the central nervous system in chicks.
Acknowledgement This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.
Fig. 4. Effects of nor-binaltorphimine (nor-BNI) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 8; nor-BNI, 9; NPY, 9; NPY + nor-BNI, 8.
References [1] C. Abbadie, Y.X. Pan, G.W. Pasternak, Differential distribution in rat brain of mu opioid receptor carboxy terminal splice variants MOR-
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K.-I. Dodo et al. / Neuroscience Letters 373 (2005) 85–88 1C-like and MOR-1C-like immunoreactivity; evidence for regionspecific processing, J. Comp. Neurol. 419 (2000) 244–256. R.J. Bodnar, Opioid receptor subtype antagonists and ingestion, in: S.J. Cooper, P.G. Clifton (Eds.), Drug Receptor Subtypes and Ingestive Behavior, Academic Press, London, 1996, pp. 127–146. R.J. Bodnar, M.M. Hadjimarkou, Endogenous opiates and behavior, Peptides 23 (2002) 2307–2365. T. Boswell, Regulation of feeding by neuropeptide Y, in: A. Dawson, C.M. Chaturvedi (Eds.), Avian Endocrinology, Narosa Publishing House, New Delhi, 2002, pp. 349–360. S. Bouret, V. Prevot, D. Croix, S. Jegou, H. Vaudry, G.B. Stefano, J.C. Beauvillain, V. Mitchell, Mu-opioid receptor mRNA expression in proopiomelanocortin neurons of the rat arcuate nucleus, Mol. Brain Res. 70 (1999) 155–158. T. Bungo, K. Kawamura, T. Izumi, K.-I. Dodo, H. Ueda, Feeding responses to -, ␦- and -opioid receptor agonists in the meat-type chick, Pharmacol. Biochem. Behav. 78 (2004) 707–710. J.T. Clark, P.S. Kalra, W.R. Crowley, S.P. Karla, Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats, Endocrinology 115 (1984) 427–429. J.L. Davis, D.T. Masuoka, J.F. Gerbrandt, A. Cherkin, Autoradiographic distribution of l-proline in chicks after intracerebral injection, Physiol. Behav. 22 (1979) 693–695. B.A. Gosnell, A.S. Levine, Stimulation of ingestive behaviour by preferential and selective opioid agonists, in: S.J. Cooper, P.G. Clifton (Eds.), Drug Receptor Subtypes and Ingestive Behavior, Academic Press, London, 1996, pp. 147–166. T.L. Horvath, F. Naftolin, S.P. Kalra, C. Leranth, Neuropeptide-Y innervation of -endorphin-containing cells in the rat mediobasal hypothalamus: a light and electron microscopic double immunostaining analysis, Endocrinology 131 (1992) 2461–2467. D.C. Jewett, M.K. Grace, R.M. Jones, C.J. Billington, P.S. Portoghese, A.S. Levine, The kappa-opioid antagonist GNTI reduces U50,488-, DAMGO-, and deprivation-induced feeding, but not butorphanol- and neuropeptide Y-induced feeding in rats, Brain Res. 909 (2001) 75–80.
[12] S.P. Kalra, M.G. Dube, S. Pu, B. Xu, T.L. Horvath, P.S. Kalra, Interacting Appetite-regulating pathways in the hypothalamic regulation of body weight, Endocr. Rev. 20 (1999) 68–100. [13] T. Kotegawa, T. Takahashi, K. Tsutsui, T. Ikeda, H. Minakata, K. Nomoto, Isolation and characterization of opioid peptides in the avian brain, J. Exp. Zool. 273 (1995) 87–95. [14] C.M. Kotz, M.K. Grace, C.J. Bllington, A.S. Levine, The effect of norbinaltorphimine, -funaltrexamine and naltrindole on NPYinduced feeding, Brain Res. 631 (1993) 325–328. [15] W.J. Kuenzel, L.W. Douglass, B.A. Davison, Robust feeding following central administration of neuropeptide Y or peptide YY in chicks, Gallus domesticus, Peptides 8 (1987) 823–828. [16] S.F. Leibowitz, L. Hor, Endorphinergic and ␣-adrenergic systems in the paraventricular nucleus: Effects on eating behavior, Peptides 3 (1982) 421–428. [17] A. Mansour, C.A. Fox, S. Burke, F. Meng, R.C. Thompson, H. Akil, S.J. Watson, Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study, J. Comp. Neurol. 350 (1994) 412–438. [18] J.F. McCormack, D.M. Denbow, Feeding, drinking and temperature response to intracerebroventricular -endorphin in the domestic fowl, Peptides 9 (1988) 709–715. [19] J.F. McCormack, D.M. Denbow, Ingestive responses to mu and delta opioid receptor agonists in the domestic fowl, Br. Poult. Sci. 30 (1989) 327–340. [20] National Research Council, Guide for the Care and Use of Laboratory Animals, Department of Health and Human Services, Washington, DC, NIH Publication No. 85-23, 1985. [21] S.L. Petersen, K.D. LaFlamme, Progesterone increases levels of muopioid receptor mRNA in the preoptic area and arcuate nucleus of ovariectomized, estradiol-treated female rats, Mol. Brain Res. 52 (1997) 32–37. [22] C.J. Savory, M.J. Gentle, M.R. Yeomans, Opioid modulation of feeding and drinking in fowls, Br. Poult. Sci. 30 (1989) 379– 392.
Response of neuropeptide Y-induced feeding to -, ␦- and -opioid receptor antagonists in the neonatal chick Koh-Ichi Dodo, Tomofumi Izumi, Hiroshi Ueda, Takashi Bungo∗ Laboratory of Animal Science, Department of Agrobiological Science, Faculty of Agriculture, Ehime University, Tarumi 3-5-7 Matsuyama, Ehime 790-8566, Japan Received 2 July 2004; received in revised form 13 August 2004; accepted 27 September 2004
Abstract It is known that opioid antagonists reduce the orexigenic effect of neropeptide Y (NPY) in mammals. We studied the effect of three opioid antagonists on NPY-induced feeding in male broiler chicks. -Funaltrexamine (-FNA), naloxonazine (NAL), ICI-174,864 (ICI) or nor-binaltorphimine (nor-BNI), antagonists of -, 1 -, ␦- or -receptors, and NPY were co-injected in chicks. Food intake was measured 30 min after treatment. Co-injection of -FNA or NAL was effective in reducing NPY-induced feeding, whereas ICI and nor-BNI had little effect on NPY-induced feeding. These data suggest that the -opioid receptor, especially the 1 -opioid has some relation to NPY-induced feeding, and implies that an endogenous ligand, such as -endorphin, participates in the orexigenic effect of NPY in neonatal chicks. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Feeding behavior; Neuropeptide Y (NPY); Opioid; Chick; -Receptor; ␦-Receptor; -Receptor
Research over the past several decades has examined the brain neurochemical systems that regulate food intake in mammalian species, and have identified a number of major central neurotransmitter circuits that appear to contribute to this behavior. Opiates and neuropeptide Y (NPY), the potent stimulators of feeding behavior in the rat [7,9], are found in brain areas known to be involved in the control of ingestive behavior [3]. Similar to mammalians, both peptides have been shown to exist in various regions of chick brain [4,13]. Then, it was reported that intracerebroventricular (ICV) injection of opioids or NPY increased food intake of the chick and chicken [15,18,19,22]. For the past decade, much evidence in mammals has been collected suggesting a functional link between NPY and -endorphin (-END), one of the endogenous opioids (e.g., [10]). However, no information about the relationship between them in avian species is available. The purpose of this study was to examine the effect of each opioid receptor antagonist on NPY-induced feeding in chicks.
∗
Corresponding author. Tel.: +81 89 946 9820; fax: +81 89 946 9820. E-mail address: [email protected] (T. Bungo).
0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.09.065
Day-old male broiler chicks (Cobb) were purchased from a local hatchery (Fresh Foods, Ehime, Japan). The birds were maintained in a room with 24-h lighting and at a temperature of 30 ◦ C. They were given free access to a commercial starter diet (Nihon Nosan Kogyo Co. Ltd., Yokohama, Japan) and water during the pre-experimental period. The chicks were maintained in accordance with the recommendations of the National Research Council [20]. They were distributed into experimental groups based on their body weight so that the average body weight was as uniform as possible for each treatment. The birds were reared individually in experimental cages and had ad libitum access to food up to the time of experiments. Birds (2 or 3 days old) fed ad libitum were given diet for 30 min immediately after treatment. Food intake was determined by measuring the reduction of diet from a preweighed feeder. The weight of feeders was measured using an electric digital balance of precision ±1 mg. NPY (porcine), naloxonazine dihydrochloride (NAL; a selective 1 -opioid receptor antagonist) and norbinaltorphimine dihydrochloride (nor-BNI; a selective opioid receptor antagonist) were purchased from Sigma (St. Louis, MO, USA), and -funaltrexamine hydrochloride (-
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K.-I. Dodo et al. / Neuroscience Letters 373 (2005) 85–88
FNA; a selective -opioid receptor antagonist) and ICI174,864 (ICI; a selective ␦-opioid receptor antagonist) were obtained from Tocris Cookson (Bristol, UK). The drugs were dissolved in a 0.1% Evans Blue solution, which was prepared in 0.85% saline. Saline containing Evans Blue was used as a control. The birds were ICV injected with the solutions (10 l) using a microsyringe according to the methods used by Davis et al. [8]. Each chick was injected once only with saline, NPY, each opioid receptor antagonist or antagonist co-injected with NPY. The doses of opioid antagonists applied here were decided according to the preliminary trials, in which these doses of antagonists did not elicit any abnormal behavior (such as depression) in ad libitum chicks. At the end of the experiments, birds were sacrificed by decapitation, after which the location of the injection site was confirmed. Data from the individuals that were not verified by the presence of Evans Blue dye in the lateral ventricle were deleted. The number of birds used for data analysis is shown in each figure. Data were analyzed by two-way ANOVA with respect to the effects of NPY and each opioid antagonist. A post hoc test was done using Fisher’s LSD test. Statistical significance was set at P < 0.05. Data were expressed as means ± S.E.M. The effect of ICV co-injection of -FNA (10 g) and NPY (1 g) on food intake in broiler chicks at 30 min after injection is shown in Fig. 1. Food intake of the NPY plus -FNA group was greater than that of the control group, but was lower than that of the NPY alone group. Significant NPY [F(l,29) = 158.14, P < 0.001] and -FNA [F(l,29) = 8.562, P < 0.01] effects were observed. A significant interaction between NPY and -FNA [F(l,29) = 8.663, P < 0.01] was also detected. The effect of -FNA on NPY-induced food intake was potent, reducing NPY-induced feeding by 35% in the 0–30-min feeding interval.
Fig. 1. Effects of -funaltrexamine (-FNA) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 8; -FNA, 8; NPY, 10; NPY + -FNA, 7.
Fig. 2. Effects of naloxonazine (NAL) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 10; NAL, 7; NPY, 9; NPY + NAL, 7.
Fig. 2 shows the effect of NAL (10 g) on NPY (1 g)-induced feeding in chicks. Significant NPY [F(1,29) = 103.00, P < 0.001] and NAL [F(1,29) = 10.762, P < 0.01] effects were observed. A significant interaction between NPY and NAL [F(1,29) = 7.665, P < 0.01] was also detected. Similar to -FNA the effect of NAL on NPYinduced food intake was potent, reducing NPY-induced feeding during the experimental period. The effect of ICV co-iniection of ICI (4 g) and NPY (1 g) on food intake in chicks is shown in Fig. 3. Food intake of the NPY alone group and the NPY plus ICI group were greater than that of the control group. Significant NPY
Fig. 3. Effects of ICI-174,864 (ICI) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 11; ICI, 8; NPY, 7; NPY + ICI, 8.
K.-I. Dodo et al. / Neuroscience Letters 373 (2005) 85–88
[F(l,30) = 42.614, P < 0.001] effect was found, but no significant ICI effect [F(l,30) = 0.302, P > 0.05] or interaction between treatments [F(l,30) = 1.488, P > 0.05]. Fig. 4 shows the effect of ICV co-injection of norBNI (2 g) and NPY (1 g) on food intake in chicks. Significant NPY [F(l,30) = 107.00, P < 0.001] and nor-BNI [F(l,30) = 5.289, P < 0.05] effects were observed. Food intake of the NPY plus nor-BNI group was greater than that of the control group, but was lower than that of the NPY alone group. However, no significant interaction [F(l,30) = 0.001, P > 0.05] was detected. These results suggest that NPY-induced feeding has a relationship with the opioidergic system through the -opioid receptor in chicks (Figs. 1 and 2). In particular, the system via the 1 -opioid receptor seemed to be important for the orexigenic effect of NPY in chicks. In mammals, it is known that the -opioid receptor is subdivided into two subtypes (1 and 2 -receptor) and equally sensitive ingestive response to -FNA (both 1 - and 2 -opioid receptors) and NAL (1 opioid receptor) suggest 1 -receptor mediation of that response [2]. Although there are no report about the roles of each heteroreceptor in chicks, it is also likely that the stimulation via 1 -opioid receptor might modulate feeding regulation in chicks. As for the relationship between NPY and endogenous opioids, it is reported that NPY-producing neurons are synaptically linked with -END-producing neurons in the arcuate nucleus of rats [10]. Additionally, similar to NPY, -END injected into the hypothalamus also increased feeding in rats (e.g., [16]). It is suggested that NPY may induce feeding directly on its own and also by stimulating -END in relevant sites of the brain [12]. In the case of chickens, McCormack and Denbow [18] demonstrated that -END likewise stimulates food intake in both meat- and layer-type chickens. Thus, although the morphological link between NPY and -END in the chicken hypothalamus has not been identified, it is
87
possible that -END participates in NPY-induced feeding in chicks. Although -END is an endogenous ligand for both and ␦-opioid receptors, ␦-opioid antagonist (ICI) did not attenuate NPY-induced food intake in chicks (Fig. 3). In the preliminary trial, we found that central administration of ICI (4 g) decreased deprivation-induced feeding 30 min after presentation of food by as much as 25% (unpublished data). These results suggest that deprivation-induced feeding, but not NPY-induced feeding, might interact with the opioidergic system through the ␦-opioid receptors in chicks. This result is in agreement with a previous report, which showed that but not ␦-opioid antagonist decreased NPY-induced feeding in rats [14]. The possible reason for the ineffective ␦-opioid antagonist on NPY-induced feeding could be attributed to a lack of ␦-opioid receptors in relevant sites. In the aforementioned brain site (the arcuate nucleus), morphological studies showed that the -opioid receptor was expressed [1,5,21], while the ␦-opioid receptor was not [17]. In a previous study, we found that food intake at 30 min was increased by ICV injection of -opioid receptor agonists (U-50488H and U-62066) in chicks [6]. On the other hand, the result in this study showed that -opioid antagonist (norBNI) did not attenuate NPY-induced food intake in chicks (Fig. 4). Similar to this result, GNTI (a newly synthesized antagonist selective for -opioid receptors) was ineffective in reducing the orexigenic effect of NPY in rats [11]. Accordingly, it is unlikely that an endogenous ligand for the -opioid receptor, such as dynorphin, might participate in NPY-induced feeding in both chicks and rats. Recently, Boswell [4] has revealed the existence of nutritionally sensitive neurons expressing NPY in the hypothalamic infundibular nucleus of birds that appear to be neuroanatomically equivalent to NPY neurons in the arcuate nucleus of the mammalian hypothalamus. Thus, it is likely that the linkage (NPY--END) in chicks may exist in the infundibular nucleus. Clearly, further work for neuroanatomical research is necessary in chickens. However, the results presented here suggest that the opioidergic system through the 1 -opioid receptor, especially the 1 -opioid, has a relationship with the orexigenic effect of NPY in chicks. Additionally, NPY may stimulate the release and/or synthesis of -END in the central nervous system in chicks.
Acknowledgement This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science.
Fig. 4. Effects of nor-binaltorphimine (nor-BNI) on NPY-induced food intake in chicks. Values are means ± S.E.M. Means with different letters are significantly different at P < 0.05. The number of chicks used were: saline, 8; nor-BNI, 9; NPY, 9; NPY + nor-BNI, 8.
References [1] C. Abbadie, Y.X. Pan, G.W. Pasternak, Differential distribution in rat brain of mu opioid receptor carboxy terminal splice variants MOR-
88
[2]
[3] [4]
[5]
[6]
[7]
[8]
[9]
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