'Compulsive' lever-pressing in rats is attenuated by the serotonin re-uptake inhibitors paroxetine and fluvoxamine but not by the tricyclic antidepressant desipramine or the anxiolytic diazepam

D. Joel, E. Ben-Amir, J. Doljansky, S. Flaisher

Research output: Contribution to journalArticlepeer-review

Abstract

Rats undergoing extinction of lever-pressing for food after the attenuation of an external feedback for this behavior, exhibit excessive lever-pressing unaccompanied by an attempt to collect a reward, which may be analogous to the excessive and unreasonable behavior seen in obsessive-compulsive disorder (OCD). Given that one of the most salient features of OCD is its selective response to treatment with serotonin re-uptake inhibitors (SRIs), the present study compared the effects of the SRIs paroxetine and fluvoxamine on compulsive lever-pressing, with those of the tricyclic antidepressant, dssipramine, and the benzodiazepine, diazepam, which are not effective in the treatment of OCD. Paroxetine (1-15 mg/kg) and fluvoxamine (10-20 mg/kg) dose-dependently reduced the number of compulsive lever-presses and the number of lever-presses followed by an attempt to collect a reward; desipramine (5-15 mg/kg) dose-dependently reduced only the number of lever-presses followed by an attempt to collect a reward; diazepam (2-10 mg/kg) did not affect either type of lever-pressing, except for the highest dose (10 mg/kg), which almost completely abolished lever-press responding. When administered in an extinction session not preceded by signal attenuation, paroxetine, fluvoxamine and desipramine affected only the number of lever-presses followed by an attempt to collect a reward, whereas diazepam (4-8 mg/kg) decreased both types of lever-presses. The present findings strengthen the suggestion that compulsive lever-pressing may serve to model compulsive behavior in OCD, and lends the model predictive validity.

Original languageEnglish
Pages (from-to)241-252
Number of pages12
JournalBehavioural Pharmacology
Volume15
Issue number3
StatePublished - May 2004

Keywords

  • Animal model
  • Extinction
  • Lever-press
  • OCD (obsessive-compulsive disorder)
  • Post-training signal attenuation
  • Rat

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