Transcranial direct current stimulation (tDCS) reverses the initial paradoxical effects of paroxetine in olfactory bulbectomized adolescent rats

Abstract

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that sends weak electrical current through the skull, resulting in neuroplastic changes. We examined its antidepressant properties using adolescent rats, as current antidepressant drug treatment during pre-pubescent stages often proves ineffective and may also result in worsening of depressive symptoms. We induced a depressive-like phenotype in adolescent Sprague-Dawley rats using olfactory bulbectomy (OBX), a rodent model of depression that results in behavioural and neurochemical changes that are reversed by antidepressant treatment. We examined if acute (two days) or chronic (two weeks) tDCS treatment resulted in reductions of OBX-induced depressive-like behavioural symptoms, including hyperlocomotion in an open field chamber, latency to feed in a novelty suppressed feeding test, immobility in a forced swim test, and deceased sucrose consumption, and if these effects were achievable with tDCS alone or in combination with paroxetine, a selective serotonin reuptake inhibitor. Finally, we examined whether the antidepressant-like activity of tDCS is linked to its capacity to increase the growth-stimulating protein brain-derived neurotrophic factor (BDNF) by collecting blood plasma for an enzyme-linked immunosorbent assay (ELISA). We found that both OBX surgery and paroxetine treatment increased depressive-like behaviours in adolescent rats, and that tDCS reversed these effects. Furthermore, OBX resulted in a decrease in plasma BDNF, an effect that was resistant to both tDCS and paroxetine treatment. Overall, our results suggest that tDCS is an effective adjunct treatment for adolescent depression in combination with antidepressant drugs.