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Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Effects of morphine alone and in combination with naloxone or d-amphetamine on shock-maintained behavior in the
Abstract:
Key-pressing behavior in the squirrel monkey was maintained under an 8-min fixed-interval (FI) schedule of electric-shock delivery. The acute i.m. administration of morphine prior to a daily session decreased response rates at doses of 1.0--3.0 mg/kg but had little systematic effect on rate at doses of 0.03-0.3 mg/kg. When naloxone was administered concomitantly with morphine prior to a session, 0.01 mg/kg naloxone required a three-fold increase in the dose of morphine necessary to obtain decreased response rates, 0.1 mg/kg naloxone required a 30-fold increase in morphine, and 1.0 mg/kg required more than a 30-fold increase in morphine. Moreover, the administration of naloxone with morphine resulted in increased rates of responding at certain combinations of doses of the two drugs. The administration of d-amphetamine (0.03 or 0.1 mg/kg) alone increased mean response rates under the FI schedule; when combined with 0.03-0.3 mg/kg morphine the increases in responding were greater than obtained with d-amphetamine alone. The negative slope of the linear regression lines relating the effects of morphine to control rates of responding engendered under the FI schedule was decreased when morphine was combined with naloxone, but not with d-amphetamine. These results show that naloxone, but not d-amphetamine, can antagonize the response-rate decreasing effect of morphine when responding in the squirrel monkey is maintained by response-produced electric shock.
Insights
Naloxone antagonizes morphine-induced decreases in key-pressing behavior in squirrel monkeys under an electric shock schedule. D-amphetamine, however, potentiated morphine's effects, highlighting differential drug interactions.
Area of Science:
- Behavioral pharmacology
- Neuroscience
- Animal models
Background:
- Squirrel monkeys exhibit key-pressing behavior maintained by electric shock.
- Morphine's effects on behavior can be dose-dependent and modulated by other drugs.
Purpose of the Study:
- To investigate the antagonistic effects of naloxone and the potentiating effects of d-amphetamine on morphine-induced behavioral changes in squirrel monkeys.
- To examine drug interactions under a fixed-interval schedule of shock delivery.
Main Methods:
- Squirrel monkeys were trained on an 8-min fixed-interval schedule of electric shock delivery.
- Morphine was administered alone or in combination with naloxone or d-amphetamine.
- Response rates were measured to assess drug effects.
Main Results:
- Morphine decreased response rates at higher doses (1.0-3.0 mg/kg) but not lower doses (0.03-0.3 mg/kg).
- Naloxone dose-dependently antagonized morphine's rate-decreasing effects, requiring significantly higher morphine doses for the same effect.
- D-amphetamine potentiated morphine's rate-increasing effects when combined.
- Naloxone decreased the negative slope of the morphine dose-response curve, while d-amphetamine did not.
Conclusions:
- Naloxone effectively antagonizes the response-rate decreasing effects of morphine in squirrel monkeys under shock-maintained responding.
- D-amphetamine does not antagonize morphine's effects and may potentiate certain behavioral outcomes.
- These findings elucidate the distinct interactions between opioids, opioid antagonists, and stimulants in a behavioral context maintained by aversive stimuli.
