Abstract | RATIONALE: Social isolation (SI) of rats directly after weaning is a non-pharmacological, non-lesion animal model based on the neurodevelopmental hypothesis of schizophrenia. The model causes several neurobiological and behavioral alterations consistent with observations in schizophrenia. OBJECTIVES: In the present study, we evaluated if isolated rats display both a pre-pulse inhibition (PPI) deficit and hyperactivity. Furthermore, the sensitivity of SI hyperactivity to antipsychotic was evaluated. METHODS: Rats were socially isolated or group-housed for 12 weeks starting on postnatal day 25. In one batch of animals, the PPI and hyperactivity response were repeatedly compared. Furthermore, we investigated the robustness of the SI-induced hyperactivity by testing close to 50 batches of socially isolated or group-housed rats and tested the sensitivity of the assay to first- and second-generation antipsychotics, haloperidol, olanzapine, and risperidone, as well as the group II selective metabotrobic glutamate receptor agonist ( LY404039). RESULTS: Socially isolated rats showed a minor PPI deficit and a robust increase in hyperactivity compared with controls. Furthermore, SI-induced hyperactivity was selectively reversed by all antipsychotics, as well as the potential new antipsychotic, LY404039. CONCLUSION: SI-induced hyperactivity was more pronounced and robust, as compared with SI-induced PPI deficits. Furthermore, SI-induced hyperactivity might be predictive for antipsychotic efficacy, as current treatment was effective in the model. Finally, using LY404039, a compound in development against schizophrenia, we have shown that the hyperactivity assay is sensitive to potential novel mechanisms of action. Thus, SI-induced hyperactivity might be a robust and novel in vivo screening assay of antipsychotic efficacy.
|
Authors | Katrine Fabricius, Lone Helboe, Anders Fink-Jensen, Gitta Wörtwein, Björn Steiniger-Brach |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 215
Issue 2
Pg. 257-66
(May 2011)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 21193984
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Acoustic Stimulation
(adverse effects)
- Analysis of Variance
- Animals
- Animals, Newborn
- Antipsychotic Agents
(pharmacology, therapeutic use)
- Behavior, Animal
- Cohort Studies
- Dose-Response Relationship, Drug
- Hyperkinesis
(drug therapy, physiopathology)
- Inhibition, Psychological
- Male
- Motor Activity
(drug effects)
- Psychoacoustics
- Random Allocation
- Rats
- Social Isolation
(psychology)
- Time Factors
|