The
orexin neuropeptides have an important role in the regulation of the sleep/wake cycle and foraging, as well as in reward processing and emotions. Furthermore, recent research implicates the
orexin system in different behavioral endophenotypes of neuropsychiatric diseases such as social avoidance and cognitive flexibility. Utilizing
orexin-deficient mice, the present study tested the hypothesis that
orexin is involved in two further mouse behavioral endophenotypes of neuropsychiatric disorders, i.e., sensorimotor gating and
amphetamine sensitivity. The data revealed that
orexin-deficient mice expressed a deficit in sensorimotor gating, measured by prepulse inhibition of the startle response.
Amphetamine treatment impaired prepulse inhibition in wildtype and heterozygous
orexin-deficient mice, but had no effects in homozygous
orexin-deficient mice. Furthermore, locomotor activity and center time in the open field was not affected by
orexin deficiency but was similarly increased or decreased, respectively, by
amphetamine treatment in all genotypes. These data indicate that the
orexin system modulates prepulse inhibition and is involved in mediating
amphetamine's effect on prepulse inhibition. Future studies should investigate whether pharmacological manipulations of the
orexin system can be used to treat neuropsychiatric diseases associated with deficits in sensorimotor gating, such as
schizophrenia or
attention deficit hyperactivity disorder.