Co-administration of fluoxetine and WAY100635 improves short-term memory function

The aim of this study was to determine whether the action of the antidepressant fluoxetine or the anxiolytic buspirone could be modified by specific 5-hydroxytriptamine (5-HT_1A) receptor blockade in a short-term memory paradigm. Male Wistar rats were trained to perform the putative short-term memory task, delayed non-matching to position. WAY100635, a selective 5-HT_1A receptor antagonist (0.15 mg/kg), was administered 15 min before either the selective serotonin reuptake inhibitor fluoxetine (3 mg/kg), or the partial 5-HT_1A receptor agonist and dopamine D2 receptor antagonist, buspirone (0.3 mg/kg). 8-Hydroxy-di-n-propylamino tetralin (8-OH-DPAT), a full 5-HT_1A receptor agonist (0.3 mg/kg), was also included in the study as a positive control. WAY100635 alone had no effect on any behavioural parameter measured (response accuracy, delay lever press activity and trial completion). 8-OH-DPAT impaired response accuracy in a delay-dependent manner, an effect reversed by WAY100635. Fluoxetine also impaired response accuracy delay-dependently. WAY100635 pretreatment not only reversed this deficit but improved response accuracy, in the presence of a significant deficit in trial completion. At the dose used, buspirone showed no significant differences compared to the control group. The data suggest that fluoxetine impairs short-term memory function by the indirect activation of 5-HT_1A receptors, but that its co-administration with WAY100635 improves short-term memory function.