Differential effect of clomipramine on habituation and prepulse inhibition in dominant versus subordinate rats

Many patients with depression have comorbidities associated with an impairment of sensorimotor gating, such as e.g. schizophrenia, Parkinson Disease, or Alzheimer disease. Anti-depressants like clomipramine that modulate serotonergic or norepinephrinergic neurotransmission have been shown to impact sensorimotor gating, it is therefore important to study potential effects of clomipramine in order to rule out an exacerbation of sensorimotor gating impairment. Prior studies in animals and humans have been inconclusive. Since serotonin and norepinephrine levels are closely related to anxiety and stress levels and therefore to the social status of an animal, we tested the hypothesis that acute and chronic effects of clomipramine on sensorimotor gating are different in dominant versus subordinate rats, which might be responsible for conflicting results in past animal studies. We used habituation and prepulse inhibition (PPI) of the acoustic startle response as operational measures of sensorimotor gating. After establishing the dominant animal in pair-housed male rats, we injected clomipramine for two weeks and measured acute effects on baseline startle, habituation and PPI after the first injection and chronic effects at the end of the two weeks. Chronic treatment with clomipramine significantly increased habituation in subordinate rats, but had no effect on habituation in dominant animals. Furthermore, PPI was slightly enhanced in subordinate rats upon chronic treatment while no changes occurred in dominant animals. We conclude that the social status of an animal, and therefore the basic anxiety/stress level determines whether or not clomipramine has a beneficial effect on sensorimotor gating and discuss possible underlying mechanisms.