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Interaction between antidepressants andd-amphetamine on variable-interval performance

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Four experiments were carried out investigating the interactions between some antidepressant drugs (imipramine, desipramine, fluvoxamine, trazodone (4 and 8 mg/kg) andd-amphetamine (0.1–3.2 mg/kg) on operant behaviour maintained under a variable-interval 80-s schedule of sucrose reinforcement; each experiment employed 12 rats.d-Amphetamine exerted a dose-related suppressant effect on response rate. Imipramine and desipramine given alone had no effect on response rate, whereas fluvoxamine (both doses) and the higher dose of trazodone produced significant increases in response rate. Pretreatment with imipramine, desipramine or fluvoxamine significantly potentiated the suppressant effect ofd-amphetamine on responding; pretreatment with trazodone had no significant effect. The potentiating effect of imipramine and desipramine may be related to their well known uptake blocking actions. The fact that fluvoxamine, a selective inhibitor of 5-hydroxytryptamine (5HT) uptake, also potentiated the effect ofd-amphetamine suggests that the suppressant effect ofd-amphetamine on operant behaviour may involve 5HT as well as catecholamine release. The lack of effect of trazodone may reflect its failure to influence uptake mechanisms. On the basis of a formal model couched in terms of Herrnstein's (1970) equation, it is suggested that imipramine, desipramine and fluvoxamine may have enhancedd-amphetamine's ability to reduce response capacity; it is suggested that the data do not provide evidence for an interaction between the antidepressants and the putative “motivation-enhancing” effect ofd-amphetamine.

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Correspondence to C. M. Bradshaw.

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Shah, K., Bradshaw, C.M. & Szabadi, E. Interaction between antidepressants andd-amphetamine on variable-interval performance. Psychopharmacology 100, 548–554 (1990). https://doi.org/10.1007/BF02244010

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Key words

  • Antidepressants
  • d-Amphetamine
  • Operant behaviour
  • Herrnstein's equation
  • Variable-interval schedules