Depression-like deficits in rats improved by subchronic modafinil

Abstract

Rationale: Attentional and sensorimotor gating deficits in human depression are observed as residual symptoms irrespective of antidepressant treatment. Clinical studies point to a benefit of modafinil in depression. No data are available on modafinil effects in depression-like animal models.

Objectives: We investigated effects of modafinil on attention and sensorimotor gating after subchronic treatment during a restraint stress protocol inducing depression-like changes in rats.

Materials and methods: Effects of modafinil were investigated (a) acutely in the forced swim test (FST) 1 h after administration of drug or placebo and (b) in a further experiment on cognition-related behaviour in rats after induction of depression-like changes using a restraint stress protocol for 15 days. Beginning from day 10, one restrained (R) and one non-restrained (NR) group were treated with modafinil (R-M and NR-M groups) and two groups with placebo (R-P and NR-P groups). At the end of protocol, behavioural testing was performed under conditions of nearly drug-free plasma. Depression-like behaviour was examined in the FST. Selective attention and sensorimotor gating were investigated as social novelty discrimination (SND) and prepulse inhibition (PPI) of acoustic startle response.

Results: Restraint led to reduced body weight, decreased mobility in the FST and impaired cognitive capabilities in the SND and the PPI. Subchronic modafinil treatment reversed restraint-induced deficits in the FST, the SND and PPI, whereas it was without effect on body weight.

Conclusions: The improvement of impaired attentional and information-processing functions under depression-like conditions suggests a benefit of modafinil in treatment of cognitive residual symptoms in affective disorders.