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 (μ), naltrindole (δ) and norbinaltorphimine (κ). TCTAP, at the highest dose tested (i.e. 5.0 nmol) and norbinaltrophimine, 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 norbinaltrophimine have no efefct on thresholds for lateral hypothalamic self-stimulation. This suggests that μ and κ opioid activity are associated with feeding, rather than 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 produce a 'naloxone-like' pattern of threshold elevation, suggesting that μ and κ receptors are involved in the process whereby endogenous opioid activity sustains feeding once initiated. © 1994.
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