Effect of gabapentin on sleep-deprivation-induced disruption of prepulse inhibition.

Abstract

There are controversial reports on the effects of gabapentin in respect to psychotic symptoms. Prepulse inhibition of the acoustic startle response is an operational measure of sensorimotor gating. In laboratory rodents, deficits in sensorimotor gating are used to model behavioral endophenotypes of schizophrenia. Sleep deprivation disrupts prepulse inhibition and can be used as a psychosis model to evaluate effects of gabapentin. This study aimed to investigate behavioral effects of gabapentin in both naïve and sleep-deprived rats. Sleep deprivation was induced in male Wistar rats by using the modified multiple platform technique in a water tank for 72h. The effect of water tank itself was studied in a sham group. The effects of oral acute and subchronic (4.5days) gabapentin doses (25, 100, or 200mg/kg/day) on sensorimotor gating and locomotor activity was evaluated by prepulse inhibition test and locomotor activity test, respectively. Plasma gabapentin levels of some groups and body weights of all groups were also assessed. Sleep deprivation disrupted prepulse inhibition, increased locomotor activity, reduced gabapentin plasma levels, and body weights. Some gabapentin doses disrupted sensorimotor gating irrespective of sleep condition. Some gabapentin doses increased locomotor activity in non-sleep-deprived rats and decreased locomotor activity in sleep-deprived rats. On the contrary, gabapentin did not normalize sleep deprivation-induced disruption in sensorimotor gating. Sleep deprivation via modified multiple platform technique could be used as an animal model for psychosis. Gabapentin may have dose- and duration-dependent effects on sensorimotor gating and locomotor activity.