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The effects of levo-alpha-acetylmethadol and its metabolites on schedule-controlled behavior in the pigeon
Abstract:
The effects of orally administered levo-alpha-acetylmethadol (LAAM) on the schedule-controlled behavior of the pigeon were compared with those of methadone. Both LAAM and methadone decreased rates of responding under a multiple fixed-interval 5-min, fixed-ratio 30-response schedule of food presentation. Although LAAM had a longer duration of action than methadone, both drugs were similar in the onset and potency of their behavioral effects. The chronic administration of either LAAM or methadone produced tolerance to the respective behavioral effects of each drug. In one set of experiments, the behavioral effects of intramuscularly administered LAAM were compared with those of its active metabolites, levo-alpha-noracetylmethadol and levo-alpha-dinoracetylmethadol. All three drugs decreased rates of responding under both components of the multiple schedule. The onset of these rate-decreasing effects was rapid and the order of potency for the production of these rate-decreases was levo-alpha-noracetylmethadol greater than levo-alpha-dinoracetylmethadol greater than or equal to LAAM. The rate-decreasing effects of LAAM and its metabolites were typical narcotic effects as defined by their reversal by naloxone.
Insights
Levo-alpha-acetylmethadol (LAAM) and methadone reduce pigeon responding rates, with LAAM showing a longer duration of action. Tolerance develops with chronic use, and LAAM
Area of Science:
- Behavioral Pharmacology
- Neuroscience
- Addiction Research
Background:
- Opioid medications like methadone are used for pain management and opioid use disorder treatment.
- Levo-alpha-acetylmethadol (LAAM) is an opioid agonist with a longer duration of action than methadone.
- Understanding the behavioral pharmacology of LAAM and its metabolites is crucial for clinical applications.
Purpose of the Study:
- To compare the behavioral effects of orally administered LAAM and methadone in pigeons.
- To investigate the duration of action, onset, and potency of LAAM versus methadone.
- To examine the development of tolerance to LAAM and methadone with chronic administration.
- To compare the effects of intramuscularly administered LAAM with its active metabolites.
Main Methods:
- Pigeons were trained to perform on a multiple fixed-interval 5-min, fixed-ratio 30-response schedule of food presentation.
- Levo-alpha-acetylmethadol (LAAM) and methadone were administered orally, and their effects on response rates were measured.
- Chronic administration protocols were used to assess tolerance development.
- Intramuscular administration of LAAM and its metabolites (levo-alpha-noracetylmethadol, levo-alpha-dinoracetylmethadol) was conducted.
Main Results:
- Both orally administered LAAM and methadone decreased response rates, with similar onset and potency but longer duration for LAAM.
- Chronic administration of either drug led to tolerance to their respective behavioral effects.
- Intramuscularly administered LAAM and its metabolites also decreased response rates.
- The potency order for rate-decreasing effects was levo-alpha-noracetylmethadol > levo-alpha-dinoracetylmethadol ≥ LAAM.
- The rate-decreasing effects of LAAM and its metabolites were antagonized by naloxone, indicating typical narcotic effects.
Conclusions:
- LAAM and methadone exhibit similar acute behavioral effects in pigeons, with LAAM possessing a longer duration of action.
- Tolerance develops to the behavioral effects of both LAAM and methadone upon chronic administration.
- LAAM's active metabolites contribute to its overall pharmacological profile, with varying potencies.
- The observed effects are consistent with typical narcotic actions, reversible by naloxone.