Propofol Counteracts Depression-like Behaviors And Sleep Disturbance

Depression is a common disease with sleep disturbance that seriously limits psychosocial and decreases life quality.Characteristic sleep changes in depression include disinhibition of rapid eye movement(REM)sleep and shortage of REM sleep latency,indicating that depression and sleep disturbance are comorbid condition.The lateral habenula has emerged as an essential brain region in regulating the depression-like behaviors and sleep disturbance.Neurons in the lateral habenula contain GABA and NMDA receptors.Propofol is a unique anesthetic that engages GABA and NMDA receptors.It is utilized in clinical treatment for procedural sedation and hypnosis.Clinical research has shown that propofol triggers rapid and durable antidepressant effect.The purpose of the present study aims to reveal the role and mechanism of propofol’s antidepressant efficiency.Methods: Mice were injected with reserpine(6 mg/kg),monoamine neurotransmitter depletion agent,for depressive animal models.Behavioral tests of forced swimming test,sucrose preference test and tail suspension test,as well as the electrophysiological techniques including electroencephalogram and electromyogram recording for cortical electroencephalogram power spectrum and sleep-wake states analysis were employed to evaluate the effect of propofol on depression-like behaviors and sleep disturbance.Furthermore,immunohistochemistry of c-Fos was performed to identify the activated neurons induced by reserpine and propofol in the lateral habenula and dorsal raphe nucleus.Results: Reserpine caused depression-like behaviors,which was characterized by increasing immobility time in forced swimming and tail suspension test,as well as decreasing sucrose preference in sucrose preference test.75 and 50 mg/kg of propofol antagonized the related depression-like behaviors,which were similar to clomipramine,while 30 mg/kg of propofol had no significant effect.Reserpine induced abbreviated latency of REM sleep and increased REM sleep amount with augmented episode number.Propofol counteracted reserpine-induced sleep-wake states through increasing REM sleep latency and NREM(non-REM)sleep and diminishing REM sleep amount.Propofol significantly reduced the number of Fos immunoreactive(-ir)neurons in the lateral habenula caused by reserpine.Conclusions: Propofol counteracts reserpine-induced depression-like behaviors and sleep disturbance through acting on the lateral habenula.The evidence suggests that the lateral habenula may be a key center of propofol for regulating depression-like behaviors and sleep disturbance.