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Changes in brain norepinephrine associated with sensitization to d-amphetamine

P H Short, L Shuster

    Psychopharmacology
    |July 9, 1976
    PubMed
    Summary
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    Amphetamine pretreatment increases behavioral response and depletes norepinephrine in mice. This sensitization persists for weeks, suggesting a link between norepinephrine depletion and amphetamine

    Area of Science:

    • Neuroscience
    • Pharmacology
    • Behavioral Science

    Background:

    • Amphetamine is a psychostimulant drug with known effects on behavior and neurotransmitter systems.
    • Sensitization to amphetamine, an increased response after repeated exposure, is a key phenomenon in understanding drug addiction.
    • Norepinephrine and dopamine are critical catecholamines involved in regulating arousal, motivation, and motor activity.

    Purpose of the Study:

    • To investigate the relationship between amphetamine-induced behavioral sensitization and changes in brain catecholamine levels.
    • To determine the duration of amphetamine sensitization and its effect on norepinephrine and dopamine.
    • To explore the role of norepinephrine depletion in the development of amphetamine sensitization.

    Main Methods:

    Related Experiment Videos

  • B6AF1/J mice were pretreated with d-amphetamine HCl to induce sensitization.
  • Locomotor activity and running responses were measured after a test dose of amphetamine.
  • Whole-brain norepinephrine and dopamine levels were quantified using biochemical assays.
  • Effects of reserpine pretreatment on amphetamine response were also examined.

    • Main Results:

    • Amphetamine pretreatment significantly increased the running response to a subsequent amphetamine dose.
    • Pretreatment led to a marked decrease in whole-brain norepinephrine levels, which persisted for 25 days.
    • Dopamine levels remained largely unchanged, and no cross-sensitization to morphine or cocaine was observed.
    • Reserpine pretreatment also enhanced amphetamine-induced locomotor activity.

    Conclusions:

    • Amphetamine-induced behavioral sensitization is strongly associated with the depletion of brain norepinephrine.
    • The observed norepinephrine depletion and behavioral sensitization are long-lasting effects.
    • These findings highlight the critical role of the norepinephrine system in the neuroadaptations underlying amphetamine sensitization.