Dose-dependent and opposite effects of orexin A on prepulse inhibition response in sleep-deprived and non-sleep-deprived rats

Abstract

Orexin is a novel neurotransmitter released from lateral hypothalamus, that is a crucial modulator in sleep/wakefulness system. Recent studies also suggest its possible role in the neurodevelopmental disorders, such as schizophrenia. Our study consists of two experiments, where we investigate the effect of orexin A (OXA), one of two isoforms of orexin that can pass blood brain barrier, on the prepulse inhibition of acoustic startle reflex. The first experiment tested the effect of OXA on PPI response of non-sleep-deprived rats via intraperitoneal injection 30min before testing. Our results show that 40μg/kg OXA attenuates PPI% at 78dB and 86dB prepulse intensities. The second experiment utilized 72-h REM sleep deprivation, as a model for sleep-deprivation-induced impairment of PPI response. Here, we tested the effect of OXA on PPI% of sleep-deprived rats via intraperitoneal injection at the last 30min of sleep deprivation, testing for PPI immediately afterwards. Our results showed that (1) sleep deprivation attenuates the PPI% at 74dB, 78dB and 86dB prepulse intensities and (2) 10μg/kg OXA completely restores the impaired PPI% at 78dB only, where the highest PPI% impairment was observed. These results suggest that orexin A modulates PPI response in rats in a dose-dependent manner, oppositely for non-sleep-deprived and sleep-deprived rats, and a more detailed investigation for the etiology of this effect should follow.