This competitive renewal examines the involvement of opioid receptor subtypes on ingestive behaviors related to issues of obesity, appetite control, regulatory challenges and palatability. Inhibition of ingestive behavior in rats by general opiate receptor antagonists failed to specify the subtypes involved. Specific antagonists of the mu (beta- funaltrexamine; B-FNA), mu1 (naloxonazine), kappa (nor-binaltor-phamine; Nor-BNI) and delta ([D-Ala2, Leu5, Cys6]-enkephalin (DALCE); naltrindole) opioid receptor subtypes were employed in the original grant. The rank- order potencies of inhibition of intake by opioid receptor subtype antagonists are: a) free feeding (general = kappa is greater than mu = mu1 which is much greater than delta); b) deprivation feeding (general = mu = mu1 which is greater than kappa which is much greater than delta); c) 2- deoxy-D-glucose hyperphagia (mu2 greater than general = kappa which is much greater than delta which is greater than mu1); d) insulin hyperphagia (mu2 is much greater than general which is greater than kappa = delta = mu1); e) high-fat intake (kappa is greater than general which is greater than mu2 that is greater than delta which is greater than mu1); f) sucrose intake (general = kappa which is greater than mu2 which is greater than delta = mu1) and g) water deprivation intake (general is greater than mu2 which is greater than kappa which is much greater than delta = mu1). This competitive renewal will evaluate the effects of B-FNA, naloxonazine, Nor- BNI, DALCE, naltrindole and naltrexone upon macronutrient selection, overall ingestive inputs and outputs in a metabolic cage, body temperature and locomotor activity as well as intake in sham feeding rats. The differential roles of multiple kappa receptor subtype agonists - U50, 488H (K1) and naloxone benzoylhydrazone (K3) - will be evaluated for their central stimulatory effects upon deprivation, glucoprivic and palatable intake. The above opioid receptor subtype antagonists will be evaluated for effects upon saline drinking in normal rats, and for fluid intake in rats challenged with either angiotensin II or hypertonic saline. Finally, the chronic effects of long-acting opioid receptor subtype antagonists will be evaluated for changes in intake and body weight in normal, genetically- obese or dietary-obese rats exposed to normal or palatable diets.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004194-06
Application #
2117056
Study Section
Drug Abuse Biomedical Research Review Committee (DABR)
Project Start
1989-05-18
Project End
1996-06-30
Budget Start
1994-08-01
Budget End
1995-06-30
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Queens College
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Flushing
State
NY
Country
United States
Zip Code
11367
Pinhas, Alexander; Aviel, Michael; Koen, Michael et al. (2012) Strain differences in sucrose- and fructose-conditioned flavor preferences in mice. Physiol Behav 105:451-9
Bernal, Sonia; Miner, Patricia; Abayev, Yana et al. (2009) Role of amygdala dopamine D1 and D2 receptors in the acquisition and expression of fructose-conditioned flavor preferences in rats. Behav Brain Res 205:183-90
Bernal, Sonia Y; Dostova, Irina; Kest, Asher et al. (2008) Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the acquisition and expression of fructose-conditioned flavor-flavor preferences in rats. Behav Brain Res 190:59-66
Bodnar, Richard J (2007) Endogenous opiates and behavior: 2006. Peptides 28:2435-513
Leventhal, L; Silva, R M; Rossi, G C et al. (1998) Morphine-6beta-glucuronide-induced hyperphagia: characterization of opioid action by selective antagonists and antisense mapping in rats. J Pharmacol Exp Ther 287:538-44
Burdick, K; Yu, W Z; Ragnauth, A et al. (1998) Antisense mapping of opioid receptor clones: effects upon 2-deoxy-D-glucose-induced hyperphagia. Brain Res 794:359-63
Leventhal, L; Mathis, J P; Rossi, G C et al. (1998) Orphan opioid receptor antisense probes block orphanin FQ-induced hyperphagia. Eur J Pharmacol 349:R1-3
Leventhal, L; Stevens, L B; Rossi, G C et al. (1997) Antisense mapping of the MOR-1 opioid receptor clone: modulation of hyperphagia induced by DAMGO. J Pharmacol Exp Ther 282:1402-7
Cole, J L; Berman, N; Bodnar, R J (1997) Evaluation of chronic opioid receptor antagonist effects upon weight and intake measures in lean and obese Zucker rats. Peptides 18:1201-7
Yu, W Z; Ruegg, H; Bodnar, R J (1997) Delta and kappa opioid receptor subtypes and ingestion: antagonist and glucoprivic effects. Pharmacol Biochem Behav 56:353-61

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