Electrophysiological effects of the co-administration of escitalopram and bupropion on rat serotonin and norepinephrine neurons

Clinical studies indicate that addition of bupropion to selective serotonin (5-HT) reuptake inhibitors (SSRIs) provides incremental benefit over SSRI monotherapy in depression. This study was designed to investigate the effects of co-administration of bupropion with escitalopram on the firing rate of 5-HT and norepinephrine (NE) neurons in anesthetized rats. Escitalopram (10 mg/kg/day x 2 days), given via subcutaneously (s.c.) implanted minipumps, decreased the firing of 5-HT and NE neurons by 70% and 55%, respectively. The firing of 5-HT neurons, unlike that of NE neurons, recovered after the 14-day escitalopram regimen. Bupropion, injected once daily (30 mg/kg/day, s.c. x 2 days), did not increase 5-HT firing but decreased that of NE by 55%. After 14 days of repeated bupropion administration, 5-HT firing was increased by 50%, and NE firing was back to baseline. Co-administration of escitalopram and bupropion doubled 5-HT firing after 2 and 14 days, whereas NE neurons were inhibited by 60% after 2 days, but partially recovered after 14 days. The responsiveness of 5-HT1A autoreceptors was significantly attenuated in the combination-treated rats after 2 days, indicating an early desensitization. These results provide support for contributions from 5-HT and NE mechanisms for enhanced effectiveness of combination of SSRI and bupropion treatment.