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Methods for Intravenous Self Administration in a Mouse Model
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Intravenous cocaine challenges during desipramine maintenance.

T Kosten1, F H Gawin, D G Silverman

  • 1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|November 1, 1992
PubMed
Summary

Desipramine (DMI) did not alter the cocaine "high" but reduced the desire for cocaine in participants. This suggests DMI may help reduce cocaine craving and its physiological effects.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Addiction Medicine

Background:

  • Cocaine abuse remains a significant public health issue.
  • Desipramine (DMI) is a tricyclic antidepressant with potential applications in treating substance use disorders.
  • Understanding DMI's effects on cocaine's subjective and physiological impacts is crucial for treatment development.

Purpose of the Study:

  • To investigate the effects of desipramine (DMI) maintenance on the subjective and physiological responses to intravenous cocaine challenges.
  • To assess DMI's potential to reduce cocaine craving and desire.

Main Methods:

  • A within-subjects design was employed with five participants.
  • Participants received intravenous challenges of placebo and varying doses of cocaine (0.125-0.5 mg/kg).
  • These challenges were administered during both placebo and active desipramine (DMI) maintenance (150 mg daily for ≥10 days).

Main Results:

  • Desipramine (DMI) did not alter the subjective "high" reported after cocaine infusion.
  • However, DMI significantly attenuated the "desire for cocaine" following a single cocaine dose.
  • Physiologically, DMI increased baseline heart rate but attenuated the incremental heart rate response to cocaine.

Conclusions:

  • Laboratory findings suggest desipramine (DMI) may effectively reduce cocaine craving, both during and between episodes of use.
  • Combined with clinical trial data, DMI shows promise as a therapeutic agent for cocaine abuse.
  • DMI's physiological effects include blunting the heart rate response to cocaine, indicating a potential mechanism for reducing its cardiovascular impact.