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Imipramine as a discriminative stimulus.

L Zhang1, J E Barrett

  • 1Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

The Journal of Pharmacology and Experimental Therapeutics
|December 1, 1991
PubMed
Summary

Imipramine was established as a discriminative stimulus in pigeons. Several drugs, including other antidepressants and stimulants, mimicked its effects, suggesting shared mechanisms and potential antidepressant activity via the 5-HT1A receptor.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Behavioral Science

Background:

  • Imipramine, a tricyclic antidepressant, affects multiple neurotransmitter systems.
  • Understanding its discriminative stimulus properties is crucial for elucidating its mechanism of action.

Purpose of the Study:

  • To establish imipramine as a discriminative stimulus in pigeons.
  • To investigate the pharmacological basis of imipramine's effects by testing substitution with various compounds.
  • To explore potential antidepressant activity mediated by the 5-HT1A receptor.

Main Methods:

  • Pigeons were trained to discriminate between imipramine injections and saline.
  • A range of compounds, including tricyclic antidepressants, psychomotor stimulants, and receptor-specific agents, were tested for substitution.
  • Dose-response relationships were analyzed for substituting compounds.

Main Results:

  • Tricyclic antidepressants (desipramine, amitriptyline, doxepin), psychomotor stimulants (cocaine, d-amphetamine), and certain reuptake inhibitors (tomoxetine, nomifensine) substituted for imipramine.
  • Bupropion partially substituted, while other dopamine reuptake inhibitors did not.
  • 5-HT1A receptor agonists (8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide, gepirone) partially substituted, particularly at lower imipramine doses.
  • Clonidine, ritanserin, and fluoxetine did not occasion drug-key responding.

Conclusions:

  • Imipramine's discriminative stimulus properties are shared by compounds affecting norepinephrine and serotonin reuptake.
  • Substitution by 5-HT1A agonists suggests imipramine may interact with this receptor, supporting its antidepressant effects.
  • This study successfully established imipramine as a long-term discriminative stimulus without toxicity.

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