The antidepressant drugs fluoxetine and duloxetine produce anxiolytic-like effects in a schedule-induced polydipsia paradigm in rats: Enhancement of fluoxetine's effects by the α2 adrenoceptor antagonist yohimbine

Adam J. Prus, Sean M. Mooney-Leber, Michael D. Berquist, Alan Pehrson, Nicholas P. Porter, Joseph H. Porter

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Similar to the time-course for treating depression, several weeks of administration are required for serotonin (5-HT) reuptake inhibitors to produce anxiolytic effects. Previous studies with the schedule-induced polydipsia paradigm (a putative preclinical anxiety model) have shown that repeated administration of antidepressant drugs is necessary to produce a suppression of polydipsia, which is interpreted as an anxiolytic-like effect. The present study sought to expand past findings by evaluating the selective 5-HT reuptake inhibitor (SSRI) fluoxetine and the 5-HT-norepinephrine reuptake inhibitor duloxetine in the schedule-induced polydipsia paradigm with rats. Dose combinations of the α2 adrenoceptor antagonist yohimbine with fluoxetine were also explored to determine whether α 2 adrenoceptor antagonism could enhance the anxiolytic-like effects produced by an SSRI. Fluoxetine and duloxetine significantly reduced water intake over the course of daily administrations. Daily treatment with the combination of fluoxetine and yohimbine produced a significantly greater reduction in water intake than fluoxetine alone. The present results confirmed previous findings that inhibition of 5-HT reuptake reduces water consumption in this paradigm. The results for the α 2 antagonist yohimbine (in combination with fluoxetine) also indicate that α2 adrenoceptor antagonism may significantly enhance anxiolytic-like effects of SSRIs.

Original languageEnglish
Pages (from-to)489-494
Number of pages6
JournalBehavioural Pharmacology
Volume26
Issue number5
DOIs
StatePublished - 8 Aug 2015

Fingerprint

Polydipsia
Yohimbine
Fluoxetine
Anti-Anxiety Agents
Adrenergic Receptors
Antidepressive Agents
Appointments and Schedules
Serotonin
Drinking
Duloxetine Hydrochloride
Norepinephrine
Anxiety
Depression

Keywords

  • adrenergic receptor
  • antidepressant
  • anxiety
  • anxiolytic model
  • polydipsia
  • rat

Cite this

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The antidepressant drugs fluoxetine and duloxetine produce anxiolytic-like effects in a schedule-induced polydipsia paradigm in rats : Enhancement of fluoxetine's effects by the α2 adrenoceptor antagonist yohimbine. / Prus, Adam J.; Mooney-Leber, Sean M.; Berquist, Michael D.; Pehrson, Alan; Porter, Nicholas P.; Porter, Joseph H.

In: Behavioural Pharmacology, Vol. 26, No. 5, 08.08.2015, p. 489-494.

Research output: Contribution to journalArticle

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