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Depression-like deficits in rats improved by subchronic modafinil

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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.

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Abbreviations

ADHD:

attention deficit/hyperactivity disorder

FST:

forced swim test

PPI:

prepulse inhibition

SND:

social novelty discrimination

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Acknowledgments

The authors are grateful to Mrs. A.-K. Krause and Mr. L. Feige for their excellent technical support. This work was supported by the Deutsche Forschungsgemeinschaft (KI 677/4-2) and the Interdisciplinary Center for Clinical Research at the University of Leipzig (C31).

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, University of Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany

    Ralf Regenthal & Rainer Preiss

  2. Rudolf Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany

    Holger Koch, Christian Köhler & Ute Krügel

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  1. Ralf Regenthal
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  2. Holger Koch
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  3. Christian Köhler
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Correspondence to Ute Krügel.

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Regenthal, R., Koch, H., Köhler, C. et al. Depression-like deficits in rats improved by subchronic modafinil. Psychopharmacology 204, 627–639 (2009). https://doi.org/10.1007/s00213-009-1493-8

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  • DOI: https://doi.org/10.1007/s00213-009-1493-8

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