Electrophysiological correlates of sleep disturbance induced by acute and chronic administration of d-amphetamine

Sleep disturbance is the strongest predictor of manic relapse and is considered one of the most important objective measures of treatment response in bipolar disorder (BD). However, the neurobiological mechanisms underlying sleep disturbance in BD are poorly understood. The administration of psychostimulants to rodents can trigger a number of manic-like behaviors. Therefore, the present study aims to investigate the effects of single and repeated D-amphetamine (AMPH) administration on sleep patterns in rats. Sleep was continuously monitored during light periods after single and repeated (7 days) injections of AMPH (2 mg/kg, i.p.) or saline in adult Wistar rats using electrocorticogram and electromyographic recordings. Acute injections of AMPH suppressed sleep for the first 2 h, and were followed by a gradual increase in the amount of sleep. Both slow wave sleep (SWS) and paradoxical sleep (PS) were compromised. Repeated exposure to AMPH led to a drastic disruption of the sleep-wake cycle that was mainly characterized by a decrease of PS during all time-points recorded in comparison to the saline group. Furthermore, both acute and chronic AMPH administration induced longer latencies to both SWS and PS. These findings suggest that AMPH produces profound sleep disturbances and decreases PS sleep. Given that some of these abnormalities are observed in individuals with BD, this animal model can provide a means to investigate neurobiological aspects of sleep disturbance in BD, as well as their response to mood stabilizers.