Evaluation of serotonin, noradrenaline and dopamine reuptake inhibitors on light-induced phase advances in hamster circadian activity rhythms

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for the treatment of anxiodepressive states that are often associated with perturbed circadian rhythms including, in certain patients, phase advances. Surprisingly, the influence of SSRIs upon circadian activity rhythms has been little studied in experimental models. Accordingly, this study examined the ability of SSRIs to modulate the phase-setting properties of light on circadian activity rhythms in hamsters. Their actions were compared to those of the mixed serotonin/noradrenaline reuptake inhibitor (SNRI), venlafaxine, the selective noradrenaline reuptake inhibitor, reboxetine, and the dopamine reuptake inhibitor, bupropion. Wheel-running activity rhythms were recorded in male Syrian hamsters. Drugs were administered systemically before a light stimulus that was used to advance the timing of the hamster running rhythms. Four chemically diverse SSRIs, citalopram (1-10 mg/kg, intraperitoneally), fluvoxamine (1-10), paroxetine (1-10), and fluoxetine (10 and 20), all robustly and significantly inhibited the ability of light to phase advance hamster circadian wheel-running activity rhythms. Their actions were mimicked by venlafaxine (1-10) that likewise elicited a marked reduction in phase advances. Conversely, reboxetine (1-20) and bupropion (1-20) did not exert significant effects. These data suggest that suppression of serotonin (but not noradrenaline or dopamine) reuptake by SSRIs and SNRIs modifies circadian locomotor activity rhythms in hamsters. Further, they support the notion that an inhibitory influence upon the early-morning light-induced advance in circadian activity contributes to the therapeutic effects of serotonin uptake inhibitors in certain depressed patients.