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Investigation into the specificity of the behavioral desensitization observed after repeated angiotensin II administration
Abstracts / Appetite 57S (2011) S1–S49
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tive polysaccharide taste receptor, potential T1R homodimers, or non-taste orosensory cues. Supported by: NIH R01-DC004574. doi:10.1016/j.appet.2011.05.285
increased the hedonic fat component as well as the healthy chow component in the fcHFHS diet. doi:10.1016/j.appet.2011.05.287
Lateral hypothalamic NMDA and GABAA receptors mediate feeding elicited by ipsilateral nucleus accumbens shell inhibition K.R. URSTADT 1 , S.F. ZAIDI 2 , P. KALLY 2 , B.G. STANLEY 1,2 1 Department of Psychology, University of California, Riverside, Riverside, USA 2 Department of Cell Biol. and Neurosci., University of California, Riverside, Riverside, USA
Investigation into the specificity of the behavioral desensitization observed after repeated angiotensin II administration P.J. VENTO 1 , K.P. MYERS 2 , D. DANIELS 1 1 Department of Psychology, State University of New York at Buffalo, Buffalo, USA 2 Department of Psychology, Bucknell University, Lewisburg, USA
Food intake can be elicited by NMDA receptor stimulation or GABAA receptor blockade in the lateral hypothalamus (LH). Similarly, GABAA receptor stimulation or AMPA receptor blockade in the nucleus accumbens shell (AcbSh) can produce feeding. Although a feeding-relevant functional relationship between these nuclei has been demonstrated, it is unclear whether this interaction is ipsilateral or contralateral. To explore this interaction, adult male Sprague-Dawley rats were implanted with three chronic indwelling cannulas, one into the AcbSh and two bilaterally into the LH. To evoke food intake, the GABAA receptor agonist muscimol (0.1 g) or the AMPA receptor antagonist 6,7-Dinitroquinoxaline2,3-dione (DNQX, 1.25 g) was injected into the AcbSh. To suppress the AcbSh inhibition-induced feeding, the NMDA receptor antagonist d-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5, 2.0 g) or muscimol (25 ng) was injected into the LH either ipsilateral or contralateral to the AcbSh injection site. AcbSh muscimol and DNQX separately caused increased eating within 2 h of injection and ipsilateral LH injections of D-AP5 or muscimol suppressed or blocked this increase. In contrast, injection of D-AP5 or muscimol into the contralateral LH had little or no suppressive effect. These results suggest that there is a strong ipsilateral bias in the feeding-relevant functions of the glutamate and GABAA receptor-modulated AcbShLH circuit. doi:10.1016/j.appet.2011.05.286 Neuropeptide Y sensitivity in an animal model of diet induced obesity J.K. VD HEUVEL 1 , L. EGGELS 1 , A.J. V ROZEN 2 , C. DIEPENBROEK 1 , A. KALSBEEK 1 , E. FLIERS 1 , R.A.H. ADAN 2 , S.E. LA FLEUR 1 1 Dept Endocrinol Metab, AMC-UvA, Amsterdam, Netherlands 2 Dept Neurosci Pharmacol, RMI-UMCU, Utrecht, Netherlands Neuropeptide Y (NPY) is a hypothalamic hunger peptide, which is downregulated upon food ingestion. Interestingly, rats on a free choice high-fat high-sugar (fcHFHS) diet for 1 week show paradoxically increased NPY mRNA levels despite profound hyperphagia. After 4 weeks, mRNA levels are similar to chow, but hyperphagia remains. As the mRNA levels do not explain the sustained hyperphagic behavior, we hypothesized that NPY sensitivity increases in rats on the fcHFHS diet over the course of 4 weeks. For 4 weeks, rats were subjected to chow only, a fcHFHS diet or a choice diet of fat and chow (fcHF). After 1 and 4 weeks, rats received an intracerebroventricular (ICV) injection of 1 g NPY or vehicle. Total caloric intake and individual food components (chow, fat and sugar) were determined 2 hours after ICV injection. We showed that after 1 week both fcHF and fcHFHS groups overate and showed increased response to NPY compared to chow. After 4 weeks, only fcHFHS remained hyperphagic and showed increased responsiveness to NPY compared to fcHF and chow. Moreover, in rats on fcHFHS, NPY mainly increased the preference for lard and chow, but not sugar, after both 1 and 4 weeks on the diet. In conclusion, the higher NPY responsiveness in rats on a fcHFHS diet explains their continuing hyperphagic behavior and may result from increased NPY receptor availability since NPYmRNA levels were not increased. Interestingly, NPY
Central injection of angiotensin II (AngII) robustly increases intake of water and saline, but multiple icv injections of AngII reduce its dipsogenic efficacy, without affecting saline intake. The present experiments were designed to rule out several potential non-specific effects that could possibly account for the decreased dipsogenic potency of AngII. To test for aversive properties of the desensitizing paradigm, we paired a novel flavor (vanilla or almond) with the procedure used to generate behavioral desensitization to AngII (3× 300 ng AngII, icv) or its control manipulation (3× TBS, icv). Subsequent preference tests did not detect differences in intake of the two fluids, suggesting an absence of a conditioned taste aversion. Additional studies evaluated changes in blood pressure to test for different pressor responses to AngII in control and behaviorally desensitized rats. Tail-cuff pressure recordings detected an increased pressor response by AngII, but this was not significantly different between these groups at the time that corresponds with the observed behavioral effect. Further testing showed that the behavioral desensitization that occurs after repeated AngII is specific to the angiotensin system because water intake stimulated by a test injection of AngII was reduced, but carbachol-induced drinking was unaffected. These data are consistent with a desensitization of the response rather than a less selective suppression of behavior. Supported by: NIH. doi:10.1016/j.appet.2011.05.288 Aging of vagal afferent glutamatergic neurons in the rat R. WANTY, R.C. RITTER, K. CZAJA Department of VCAPP, College of Veterinary Medicine, Washington State University, Pullman, USA It is well known that vagal afferent neurons in nodose ganglion (NG) provide a direct connection between the gastrointestinal tract and the hind brain, and glutamate plays the major role in vagal neurotransmission. However, there has been surprisingly little known on aging of vagal afferent neurons with respect to neurochemical phenotype and function. Our previous results indicate that vagal afferent neurons in NG from 6-week-old rats express NMDA receptors composed of NR1, NR2B, NR2C and NR2D subunits. It has been also shown that CCK reduced food intake by acting on vagal afferent neurons and that the non-competitive NMDA-type glutamate receptor antagonist, MK-801, increased food intake in adult rats. In order to determine the age-related changes in subunit composition of NMDA receptors, we employed immunocytochemical techniques in NG from 6-week-old, 30-week-old and 60-weekold male Sprague-Dawley rats. To address age-related functional changes in vagal neurotransmission, we studied food intake at different ages following CCK and MK-801 administration. Results of the study revealed the age-related reduction of NR2B and NR2C subunit expression in NG. Moreover, CCK reduced food intake in all studied groups and there were no significant age-related differences. In 6-week-old rats, MK-801 increased food intake by about 20% while in older rats this effect was doubled. Results of our study show that vagal afferent glutamatergic regulation of food intake changes with age, and subunit-composition of NMDA receptor of vagal afferents contributes to the changes in the glu-
S45
tive polysaccharide taste receptor, potential T1R homodimers, or non-taste orosensory cues. Supported by: NIH R01-DC004574. doi:10.1016/j.appet.2011.05.285
increased the hedonic fat component as well as the healthy chow component in the fcHFHS diet. doi:10.1016/j.appet.2011.05.287
Lateral hypothalamic NMDA and GABAA receptors mediate feeding elicited by ipsilateral nucleus accumbens shell inhibition K.R. URSTADT 1 , S.F. ZAIDI 2 , P. KALLY 2 , B.G. STANLEY 1,2 1 Department of Psychology, University of California, Riverside, Riverside, USA 2 Department of Cell Biol. and Neurosci., University of California, Riverside, Riverside, USA
Investigation into the specificity of the behavioral desensitization observed after repeated angiotensin II administration P.J. VENTO 1 , K.P. MYERS 2 , D. DANIELS 1 1 Department of Psychology, State University of New York at Buffalo, Buffalo, USA 2 Department of Psychology, Bucknell University, Lewisburg, USA
Food intake can be elicited by NMDA receptor stimulation or GABAA receptor blockade in the lateral hypothalamus (LH). Similarly, GABAA receptor stimulation or AMPA receptor blockade in the nucleus accumbens shell (AcbSh) can produce feeding. Although a feeding-relevant functional relationship between these nuclei has been demonstrated, it is unclear whether this interaction is ipsilateral or contralateral. To explore this interaction, adult male Sprague-Dawley rats were implanted with three chronic indwelling cannulas, one into the AcbSh and two bilaterally into the LH. To evoke food intake, the GABAA receptor agonist muscimol (0.1 g) or the AMPA receptor antagonist 6,7-Dinitroquinoxaline2,3-dione (DNQX, 1.25 g) was injected into the AcbSh. To suppress the AcbSh inhibition-induced feeding, the NMDA receptor antagonist d-(-)-2-Amino-5-phosphonopentanoic acid (D-AP5, 2.0 g) or muscimol (25 ng) was injected into the LH either ipsilateral or contralateral to the AcbSh injection site. AcbSh muscimol and DNQX separately caused increased eating within 2 h of injection and ipsilateral LH injections of D-AP5 or muscimol suppressed or blocked this increase. In contrast, injection of D-AP5 or muscimol into the contralateral LH had little or no suppressive effect. These results suggest that there is a strong ipsilateral bias in the feeding-relevant functions of the glutamate and GABAA receptor-modulated AcbShLH circuit. doi:10.1016/j.appet.2011.05.286 Neuropeptide Y sensitivity in an animal model of diet induced obesity J.K. VD HEUVEL 1 , L. EGGELS 1 , A.J. V ROZEN 2 , C. DIEPENBROEK 1 , A. KALSBEEK 1 , E. FLIERS 1 , R.A.H. ADAN 2 , S.E. LA FLEUR 1 1 Dept Endocrinol Metab, AMC-UvA, Amsterdam, Netherlands 2 Dept Neurosci Pharmacol, RMI-UMCU, Utrecht, Netherlands Neuropeptide Y (NPY) is a hypothalamic hunger peptide, which is downregulated upon food ingestion. Interestingly, rats on a free choice high-fat high-sugar (fcHFHS) diet for 1 week show paradoxically increased NPY mRNA levels despite profound hyperphagia. After 4 weeks, mRNA levels are similar to chow, but hyperphagia remains. As the mRNA levels do not explain the sustained hyperphagic behavior, we hypothesized that NPY sensitivity increases in rats on the fcHFHS diet over the course of 4 weeks. For 4 weeks, rats were subjected to chow only, a fcHFHS diet or a choice diet of fat and chow (fcHF). After 1 and 4 weeks, rats received an intracerebroventricular (ICV) injection of 1 g NPY or vehicle. Total caloric intake and individual food components (chow, fat and sugar) were determined 2 hours after ICV injection. We showed that after 1 week both fcHF and fcHFHS groups overate and showed increased response to NPY compared to chow. After 4 weeks, only fcHFHS remained hyperphagic and showed increased responsiveness to NPY compared to fcHF and chow. Moreover, in rats on fcHFHS, NPY mainly increased the preference for lard and chow, but not sugar, after both 1 and 4 weeks on the diet. In conclusion, the higher NPY responsiveness in rats on a fcHFHS diet explains their continuing hyperphagic behavior and may result from increased NPY receptor availability since NPYmRNA levels were not increased. Interestingly, NPY
Central injection of angiotensin II (AngII) robustly increases intake of water and saline, but multiple icv injections of AngII reduce its dipsogenic efficacy, without affecting saline intake. The present experiments were designed to rule out several potential non-specific effects that could possibly account for the decreased dipsogenic potency of AngII. To test for aversive properties of the desensitizing paradigm, we paired a novel flavor (vanilla or almond) with the procedure used to generate behavioral desensitization to AngII (3× 300 ng AngII, icv) or its control manipulation (3× TBS, icv). Subsequent preference tests did not detect differences in intake of the two fluids, suggesting an absence of a conditioned taste aversion. Additional studies evaluated changes in blood pressure to test for different pressor responses to AngII in control and behaviorally desensitized rats. Tail-cuff pressure recordings detected an increased pressor response by AngII, but this was not significantly different between these groups at the time that corresponds with the observed behavioral effect. Further testing showed that the behavioral desensitization that occurs after repeated AngII is specific to the angiotensin system because water intake stimulated by a test injection of AngII was reduced, but carbachol-induced drinking was unaffected. These data are consistent with a desensitization of the response rather than a less selective suppression of behavior. Supported by: NIH. doi:10.1016/j.appet.2011.05.288 Aging of vagal afferent glutamatergic neurons in the rat R. WANTY, R.C. RITTER, K. CZAJA Department of VCAPP, College of Veterinary Medicine, Washington State University, Pullman, USA It is well known that vagal afferent neurons in nodose ganglion (NG) provide a direct connection between the gastrointestinal tract and the hind brain, and glutamate plays the major role in vagal neurotransmission. However, there has been surprisingly little known on aging of vagal afferent neurons with respect to neurochemical phenotype and function. Our previous results indicate that vagal afferent neurons in NG from 6-week-old rats express NMDA receptors composed of NR1, NR2B, NR2C and NR2D subunits. It has been also shown that CCK reduced food intake by acting on vagal afferent neurons and that the non-competitive NMDA-type glutamate receptor antagonist, MK-801, increased food intake in adult rats. In order to determine the age-related changes in subunit composition of NMDA receptors, we employed immunocytochemical techniques in NG from 6-week-old, 30-week-old and 60-weekold male Sprague-Dawley rats. To address age-related functional changes in vagal neurotransmission, we studied food intake at different ages following CCK and MK-801 administration. Results of the study revealed the age-related reduction of NR2B and NR2C subunit expression in NG. Moreover, CCK reduced food intake in all studied groups and there were no significant age-related differences. In 6-week-old rats, MK-801 increased food intake by about 20% while in older rats this effect was doubled. Results of our study show that vagal afferent glutamatergic regulation of food intake changes with age, and subunit-composition of NMDA receptor of vagal afferents contributes to the changes in the glu-