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Beta-funaltrexamine antagonizes the discriminative stimulus effects of morphine but not naltrexone in pigeons
Abstract:
Antagonistic actions of the irreversible, mu-selective antagonist beta-funaltrexamine (beta-FNA) were evaluated in pigeons trained to discriminate among intramuscular injections of morphine (5.6 mg/kg), saline, and naltrexone (10.0 mg/kg). Beta-FNA administered alone (1.0 or 10.0 mg/kg) failed to mimic the discriminative stimulus effects of morphine or naltrexone. Beta-FNA attenuated the discriminative stimulus effects of morphine. A three-fold larger dose of morphine was required for complete generalization when pigeons were pretreated with a dose of 1.0 mg/kg beta-FNA. A dose of 10.0 mg/kg beta-FNA completely antagonized the morphine discriminative stimulus, so that pigeons responded predominantly on the saline key up to doses of morphine that suppressed responding. Doses of beta-FNA that attenuated the effects of morphine had no effect on the discriminative stimulus effects of naltrexone. These results demonstrate that, like naltrexone, beta-FNA attenuates the discriminative stimulus effects of morphine in pigeons and, at sufficiently large doses, antagonizes morphine in an unsurmountable manner. Beta-FNA does not, however, share discriminative stimulus properties with naltrexone in these pigeons, and fails to attenuate the discriminative stimulus effects of naltrexone, lending support to the suggestion that naltrexone exerts discriminative stimulus effects under these experimental conditions predominantly by a non-mu opioid mechanism.
Insights
Beta-funaltrexamine (beta-FNA), a mu-opioid antagonist, blocks morphine
Area of Science:
- Pharmacology
- Neuroscience
- Behavioral Science
Background:
- Opioid antagonists are crucial for understanding opioid receptor function.
- Beta-funaltrexamine (beta-FNA) is an irreversible, mu-selective opioid antagonist.
- Naltrexone's discriminative stimulus effects are not fully understood, potentially involving non-mu mechanisms.
Purpose of the Study:
- To investigate the antagonistic actions of beta-FNA on morphine and naltrexone in pigeons.
- To determine if beta-FNA shares discriminative stimulus properties with naltrexone.
- To elucidate the opioid receptor mechanisms underlying naltrexone's effects.
Main Methods:
- Pigeons were trained to discriminate between morphine, saline, and naltrexone injections.
- The effects of various doses of beta-FNA, alone and in combination with morphine or naltrexone, were assessed.
- Behavioral responses (key selection) were analyzed to determine drug effects.
Main Results:
- Beta-FNA alone did not mimic morphine or naltrexone stimulus effects.
- Beta-FNA dose-dependently attenuated and antagonized the discriminative effects of morphine.
- Beta-FNA did not affect naltrexone's discriminative stimulus effects, suggesting different mechanisms.
Conclusions:
- Beta-FNA acts as an effective antagonist of morphine's discriminative stimulus effects in pigeons.
- Beta-FNA does not share discriminative stimulus properties with naltrexone.
- Naltrexone's effects in this model likely involve non-mu opioid receptor pathways.