Dietary-induced Binge-like Eating Impairs Acoustic Startle Responses to Acute Nisoxetine in Male Mice

Sensorimotor gating disruptions have been noted in several psychiatric and neurodegenerative disorders. However, the involvement of sensorimotor gating processes in eating disorders has not been well characterized. Our objective was to examine the sensorimotor gating of the acoustic startle response following dietary-induced binge eating and high-fat diet (HFD) induced weight gain in male C57B/6J mice. Acute administration of the norepinephrine reuptake inhibitor, nisoxetine (0.5 and 5 mg/kg), and a dopamine reuptake inhibitor, GBR 12783 (1.6 and 16 mg/kg), were either given alone or in combination to assess norepinephrine and dopamine alterations, respectively. Male mice with repeated bouts of calorie restriction (Restrict) and with limited access to a sweetened fat food (Binge) demonstrated an escalation of intake over 2.5 weeks under standard chow conditions. Restrict Binge (RB) mice had a reduced startle response to the startle pulse (110 dB) compared with the Naive control group at 5 mg/kg nisoxetine. There was an overall effect of nisoxetine (0.5 and 5 mg/kg) to increase percent inhibition at pre-pulse (74 dB), %PP74. Under HFD conditions, the RB group did not demonstrate a binge-like eating phenotype. The RB group on HFD had a higher response to 74 dB with nisoxetine (5.0 mg/kg) compared with a combinational dose of nisoxetine (5.0 mg/kg) and GBR 12783 (1.6 mg/kg). These findings suggest that dietary conditions that promote binge-like eating can influence the central noradrenergic and dopaminergic controls of the acoustic startle response and potentially influence sensorimotor gating.