Depression-like deficits in rats improved by subchronic modafinil.
BACKGROUND
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.


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


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.
Regenthal
Ralf
R
Institute of Clinical Pharmacology, University of Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany.
Koch
Holger
H
Köhler
Christian
C
Preiss
Rainer
R
Krügel
Ute
U
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D008297:Male; D000077408:Modafinil; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects; D012149:Restraint, Physical; D055139:Sensory Gating / Q000187:drug effects; D013550:Swimming
D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil