The effects of atomoxetine and methylphenidate on the prepulse inhibition of the acoustic startle response in mice.Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 03; 54:206-15.PN
Atomoxetine (ATM) and methylphenidate (MPD) have been used for the treatment of attention deficit hyperactivity disorder (ADHD). ATM is a selective norepinephrine reuptake inhibitor, whereas MPD is a psychostimulant and acts as a norepinephrine and dopamine reuptake inhibitor. In the present study, we investigated the effects of ATM (1, 3 or 10mg/kg) and MPD (5, 10 or 20mg/kg) on pharmacological mouse models of sensorimotor gating measured by prepulse inhibition (PPI) using the acoustic startle response test. MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist, or apomorphine, a non-competitive dopamine receptor agonist, was used to induce PPI deficits. ATM (3 or 10mg/kg, s.c.) significantly attenuated the MK-801-, but not apomorphine-, induced PPI deficits. In contrast to ATM, MPD did not reverse the PPI deficits induced by either MK-801 or apomorphine. Immunostaining revealed that the number of c-Fos-immunopositive cells was increased in the nucleus accumbens following MK-801 treatment, and this was reversed by the administration of ATM (3mg/kg), but not MPD (10mg/kg). However, neither ATM nor MPD reversed the increased number of c-Fos-immunopositive cells in the nucleus accumbens following apomorphine treatment. These results suggest that the attenuating effect of ATM on the increased c-Fos immunoreactivity in the nucleus accumbens induced by MK-801 may be attributed to the PPI deficit-ameliorating effects of ATM and that ATM would be useful to treat sensorimotor gating-related disorders by improving the patient's attention span or cognitive function.