The present proposal intends to investigate the nature of opioid receptor subtype involvement in established feeding models related to obesity, regulatory changes and stress. While suppression of feeding following the opiate receptor antagonist, naloxone has been used as evidence implicating the endogenous opioids in food intake, it cannot specify opioid receptor subtype involvement given its short duration of action and its interaction with multiple opioid receptor subtypes. Naloxonazine is a potent and long-lasting opioid receptor antagonist selective for the mu1 binding site which represents a common, high-affinity binding site for both opiates and enkephalins. Recent work has demonstrated that halox-one and naloxonazine produce different effects in some feeding paradigms and similar effects in others, thereby implicating the mu1 site in some, but not all forms of feeding behavior. Further opiate receptor subtype involvement can be implied from studies using beta-FNA, which alkylates mu receptors, ICI 174864, a delta receptor antagonist, MR2266, a putative kappa receptor antagonist and beta-CNA, which alkylates all opiate receptors. The first specific aim will analyze the effectiveness of these anti-agonists upon deprivation-induced feeding across a dose range of systematic and central injections. The second specific aim will investigate the role of mu1 and other sites in long-term models of weight gain and food intake by chronically administering the above antagonists to genetically-chase rats, rats with medial hypothalamic knife cuts and rats with hypothalamic paraventricular lesions. The third specific aim will investigate the role of mu1 and other sites in short-term models of food intake by acutely administering the above antagonists to insulin-treated rats, rats receiving tail-pinch stress, and rats offered palatable foods and liquids.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
1R01DA004194-01A2
Application #
3209493
Study Section
Pharmacology I Research Subcommittee (DABR)
Project Start
1989-05-01
Project End
1992-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Queens College
Department
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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