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Cross reverse tolerance between amphetamine, cocaine and morphine.

K Hijikuro1, H Kaneto

  • 1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.

Journal of Pharmacobio-Dynamics
|September 1, 1987
PubMed
Summary
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Researchers investigated cross reverse tolerance to stimulant and opioid drugs in mice. Morphine did not develop reverse tolerance to amphetamine or cocaine, but these drugs did show reverse tolerance to morphine, indicating different drug mechanisms.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Drug Addiction Research

Background:

  • Drug tolerance is a critical factor in addiction and treatment.
  • Reverse tolerance, or sensitization, can occur with repeated drug exposure.
  • Understanding cross-tolerance mechanisms is vital for developing effective addiction therapies.

Purpose of the Study:

  • To investigate the development of cross reverse tolerance between D-amphetamine, cocaine, and morphine.
  • To compare the effects of these drugs on ambulation and swimming behaviors in mice.
  • To elucidate the differing neurobiological mechanisms underlying reverse tolerance to these substances.

Main Methods:

  • Mice were pretreated with D-amphetamine, cocaine, or morphine.
  • Subsequent challenges with these drugs assessed ambulation-accelerating and swimming-time-prolonging effects.

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  • Observed behavioral responses were analyzed to determine the presence and direction of cross reverse tolerance.

    • Main Results:

    • D-amphetamine and cocaine pretreatment did not induce reverse tolerance to morphine's effects.
    • Morphine pretreatment resulted in increased responses to subsequent D-amphetamine and cocaine administration.
    • These findings indicate an asymmetry in the development of cross reverse tolerance.

    Conclusions:

    • The mechanisms driving reverse tolerance differ between morphine and psychostimulants like D-amphetamine and cocaine.
    • This asymmetry suggests distinct neuroadaptive pathways are involved in sensitization to opioids versus stimulants.
    • Further research into these divergent mechanisms could inform targeted addiction treatment strategies.