Contextual Influences on Naltrexone Sensitization During Daily Morphine Exposure.

Area of Science:

• Pharmacology
• Neuroscience
• Behavioral Science

Background:

• Naltrexone precipitates withdrawal in morphine-dependent animals, decreasing operant responding.
• Naltrexone's effects can vary in untreated animals based on prior exposure and reinforcement schedules.
• Understanding naltrexone's behavioral effects during opioid exposure is crucial.

Purpose of the Study:

• To investigate how morphine exposure and behavioral context alter naltrexone's effects on operant responding.
• To evaluate tolerance to μ- and κ-opioid agonists during chronic morphine administration.

Main Methods:

• Squirrel monkeys were trained on a multiple schedule with food and stimulus-shock termination (SST) reinforcers.
• Drugs including morphine and naltrexone were administered to assess effects on operant responding.
• Morphine dosage and the presence of SST components were manipulated to alter dependence and behavioral context.

Main Results:

• Daily morphine administration induced tolerance to μ-opioid agonists without naltrexone sensitization.
• Altering morphine dose and SST components shifted naltrexone's dose-effect function.
• Full naltrexone sensitization occurred when SST-maintained responding was reintroduced.

Conclusions:

• Naltrexone's effects during morphine maintenance are influenced by both the level of opioid dependence and the behavioral context.
• Behavioral factors significantly modulate naltrexone's impact on operant behavior.
• These findings highlight the complex interplay of pharmacology and behavior in naltrexone's actions.