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Related Experiment Videos

Amphetamine cumulation and tolerance development: concurrent and opposing phenomena.

S B Sparber, L H Fossom

    Pharmacology, Biochemistry, and Behavior
    |March 1, 1984
    PubMed
    Summary

    Chronic amphetamine exposure in rats led to tolerance in behavioral effects, despite drug accumulation in tissues. This suggests a complex interplay between tolerance and accumulation influencing behavioral outcomes.

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    Area of Science:

    • Neuroscience
    • Pharmacology
    • Behavioral Science

    Background:

    • Repeated amphetamine administration can lead to tolerance or augmentation of behavioral effects.
    • The balance between tolerance and drug accumulation influences observed behavioral outcomes.

    Purpose of the Study:

    • To investigate the relationship between d-amphetamine distribution in tissues and its behavioral effects after acute and chronic treatment.
    • To determine the extent of tolerance and drug accumulation with repeated d-amphetamine administration.

    Main Methods:

    • Rats were trained on a fixed-ratio schedule for food reinforcement.
    • Animals received daily injections of saline or varying doses of 3H-d-amphetamine for 16 days.
    • Tissue distribution of d-amphetamine and its effects on operant responding were measured.

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    Main Results:

    • Acute d-amphetamine treatment produced dose-dependent effects on operant responding.
    • Chronic treatment with the highest dose attenuated the acute suppressant effect, indicating tolerance.
    • d-amphetamine accumulated in tissues with chronic high-dose treatment, and tolerance was observed.

    Conclusions:

    • Tolerance to the acute behavioral effects of d-amphetamine develops with chronic administration.
    • Drug accumulation in tissues occurs with chronic high-dose treatment.
    • The behavioral effects of d-amphetamine are not solely predicted by tissue concentrations after chronic exposure, indicating complex neurobiological adaptations.