title: Pharmacological characterization of social isolation-induced hyperactivity.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Synaptic Transmission2, H. Lundbeck A/S, Synaptic Transmission, Ottiliavej 9, 2500 Valby, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Fabricius
authors.forename: Lone
authors.initials: L
authors.lastname: Helboe
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
authors.forename: Gitta
authors.initials: G
authors.lastname: Wörtwein
authors.forename: Björn
authors.initials: B
authors.lastname: Steiniger-Brach
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000188:drug therapy* / Q000503:physiopathology*; D007266:Inhibition, Psychological; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011571:Psychoacoustics; D011897:Random Allocation; D051381:Rats; D012934:Social Isolation / Q000523:psychology*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents