The role of multiple opioid receptors in the maintenance of stimulation-induced feeding.
Feeding induced by lateral hypothalamic electrical stimulation is sensitive to opioid antagonism and has previously been blocked by naloxone and antibodies to dynorphin A fragments. In the present study, high affinity receptor-selective antagonists were used to determine the particular opioid receptor type(s) that mediates stimulation-induced feeding (SIF). Separate groups of rats were used to conduct i.c.v. dose-response studies with TCTAP (mu), naltrindole (delta) and norbinaltorphimine (kappa). TCTAP, at the highest dose tested (i.e. 5.0 nmol) and norbinaltorphimine, at doses of 10.0 and 50.0 nmol, increased the brain stimulation frequency threshold for eliciting SIF. Naltrindole, at doses up to 50.0 nmol, had no effect. Results of another study, recently conducted in this laboratory, indicate that the present doses of TCTAP and norbinaltorphimine have no effect on thresholds for lateral hypothalamic self-stimulation. This suggests that mu and kappa opioid activity are associated with feeding, rather than the eliciting brain stimulation, and excludes non-specific performance deficits as an explanation of elevated SIF thresholds. In the SIF test, where 5 determinations of threshold are obtained in serial order, naloxone characteristically increases thresholds toward the end of a test while conventional appetite suppressants increase thresholds uniformly throughout a test. TCTAP and norbinaltorphimine produced a 'naloxone-like' pattern of threshold elevation, suggesting that mu and kappa receptors are involved in the process whereby endogenous opioid activity sustains feeding once initiated.
Papadouka
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Millhauser Laboratories, Department of Psychiatry, New York University Medical Center, NY 10016.
Carr
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KD
D000595:Amino Acid Sequence; D000818:Animals; D004056:Differential Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000502:physiology*; D004558:Electric Stimulation; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology*
C087250:1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-cysteinyl-tyrosyl-tryptophyl-arginyl-threonyl-penicillamyl-threoninamide; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011957:Receptors, Opioid; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C055382:naltrindole