title: 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.
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 α2 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 α2 antagonist yohimbine (in combination with fluoxetine) also indicate that α2 adrenoceptor antagonism may significantly enhance anxiolytic-like effects of SSRIs.
authors.affiliation: aDepartment of Psychology, Northern Michigan University, Marquette, Michigan bExternal Sourcing and Scientific Excellence, Lundbeck Research USA Inc., Paramus, New Jersey cDepartment of Psychology, Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Prus
authors.forename: Sean M
authors.initials: SM
authors.lastname: Mooney-Leber
authors.forename: Michael D
authors.initials: MD
authors.lastname: Berquist
authors.forename: Alan L
authors.initials: AL
authors.lastname: Pehrson
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Porter
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Porter
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D060766:Drinking Water; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D005508:Food Deprivation; D008297:Male; D059606:Polydipsia / Q000188:drug therapy* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D060766:Drinking Water; D000068736:Duloxetine Hydrochloride; D005473:Fluoxetine; D018341:Receptors, Adrenergic, alpha-2; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D015016:Yohimbine