title: Increased dopaminergic activity in socially isolated rats: an electrophysiological study.
abstract: The development of animal models mimicking symptoms associated with schizophrenia has been a critical step in understanding the neurobiological mechanisms underlying the disease. Long-term social isolation from weaning in rodents, a model based on the neurodevelopmental hypothesis of schizophrenia, has been suggested to mimic some of the deficits seen in schizophrenic patients. We confirm in the present study that socially isolated rats display an increase in both spontaneous and d-amphetamine-induced locomotor activity, as well as deficits in sensorimotor gating as assessed in a pre-pulse inhibition paradigm. In addition, in vivo electrophysiological studies revealed changes in dopaminergic cell firing activity in the ventral tegmental area of isolated rats when compared to group-housed controls. These alterations include an increase in the number of spontaneously active dopaminergic neurons, and a change of firing activity towards a more irregular and bursting firing pattern. Taken together, our findings suggest that the behavioral phenotype induced by social isolation may be driven by an overactive dopamine system.
authors.affiliation: Discovery Pharmacology Research, H. Lundbeck A/S, Ottiliavej 7-9, 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
authors.forename: Florence
authors.initials: F
authors.lastname: Sotty
mesh_terms: D000200:Action Potentials; D000818:Animals; D003913:Dextroamphetamine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D005260:Female; D006185:Habituation, Psychophysiologic; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects; D012934:Social Isolation; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D003913:Dextroamphetamine; D004298:Dopamine