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Involvement of mu1 and mu2 opioid receptor subtypes in tail-pinch feeding in rats
1Department of Pharmacology, Mount Sinai School of Medicine, New York, NY 10029.
Abstract:
Tail-pinch feeding (TPF) in rats is decreased following general (naltrexone, NTX) and mu (Cys2-Tyr3-Orn5-Pen7-amide, CTOP) opioid antagonists, but not following kappa (nor-binaltorphamine. Nor-BNI) or delta (naltrindole, NTI) opioid antagonists. Because multiple mu (mu1 and mu2) and delta (delta 1 and delta 2) opioid receptor subtypes have been characterized, the present study evaluated whether TPF was differentially altered following ICV administration of general (NTX), mu (beta-funaltrexamine, B-FNA), mu1 (naloxonazine, NAZ), kappa (Nor-BNI), delta 1 ([D-Ala2, Leu5, Cys6]-enkephalin, DALCE) and delta 2 (NTI) opioid antagonists. Like the reversible mu antagonist CTOP, the irreversible mu antagonist B-FNA significantly and dose-dependently (1-20 micrograms) reduced TPF by up to 28%. In contrast, whereas NAZ (50 micrograms) reduced TPF by 32%, this effect was highly variable and failed to achieve significance. Neither NTX (5-10 mg/kg, SC), Nor-BNI (20 micrograms), DALCE (40 micrograms) nor NTI (20 micrograms) significantly altered TPF, suggesting that kappa, delta 1 and delta 2 opioid receptor subtypes were not involved. Because no antagonist altered the duration of food contact during tail pinch, it appears that the opioid effect modulates ingestive rather than activational mechanisms. The reliable inhibition of TPF by B-FNA (mu1 and mu2), together with the variable effect of naloxonazine (mu1), appears to implicate both mu binding sites in this response.
Insights
Opioid antagonists, specifically mu-selective ones like beta-funaltrexamine, reduce tail-pinch feeding in rats. This suggests mu opioid receptors play a key role in regulating ingestive behaviors, not just activation.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Tail-pinch feeding (TPF) in rats is a validated measure of ingestive behavior.
- Previous studies indicated TPF is modulated by general and mu-opioid antagonists.
- The existence of multiple opioid receptor subtypes necessitates a finer examination of their roles.
Purpose of the Study:
- To investigate the differential effects of various opioid receptor subtype antagonists on TPF.
- To determine the specific involvement of mu1, mu2, delta1, and delta2 opioid receptors in TPF.
Main Methods:
- Rats were administered various opioid antagonists intracerebroventricularly (ICV).
- Antagonists included general (naltrexone), mu (beta-funaltrexamine, naloxonazine), kappa (nor-binaltorphamine), and delta (DALCE, naltrindole) selective agents.
- Tail-pinch feeding behavior was measured and analyzed for changes.
Main Results:
- The irreversible mu-antagonist beta-funaltrexamine (B-FNA) significantly reduced TPF in a dose-dependent manner.
- The mu1-selective antagonist naloxonazine (NAZ) showed a variable reduction in TPF.
- Kappa (Nor-BNI), delta1 (DALCE), and delta2 (NTI) antagonists did not significantly alter TPF.
Conclusions:
- Mu opioid receptor subtypes (both mu1 and mu2) are implicated in the opioid-mediated regulation of TPF.
- The observed effects suggest that opioids modulate the ingestive aspects of feeding, rather than the motor activation.
- Kappa and delta opioid receptor subtypes do not appear to play a significant role in TPF.