Involvement of mu₁ and mu₂ opioid receptor subtypes in tail-pinch feeding in rats

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 (delta₁ and delta₂) 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), delta₁ ([D-Ala², Leu⁵, Cys⁶]-enkephalin, DALCE) and delta₂ (NTI) opioid antagonists. Like the reversible mu antagonist CTOP, the irreversible mu antagonist B-FNA significantly and dose-dependently (1-20 μg) reduced TPF by up to 28%. In contrast, whereas NAZ (50 μg) reduced TPF by 32%, this effect was highly variable and failed to achieve significance. Neither NTX (5-10 mg/kg, SC), Nor-BNI (20 μg), DALCE (40 μg) nor NTI (20 μg) significantly altered TPF, suggesting that kappa, delta₁ and delta₂ 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.