title: Chronic treatment with mood-stabilizers attenuates abnormal hyperlocomotion of GluA1-subunit deficient mice.
abstract: Abnormal excitatory glutamate neurotransmission and plasticity have been implicated in schizophrenia and affective disorders. Gria1-/- mice lacking GluA1 subunit (encoded by Gria1 gene) of AMPA-type glutamate receptor show robust novelty-induced hyperactivity, social deficits and heightened approach features, suggesting that they could be used to test for anti-manic activity of drugs. Here, we tested the efficacy of chronic treatment with established anti-manic drugs on behavioural properties of the Gria1-/- mice. The mice received standard mood stabilizers (lithium and valproate) and novel ones (topiramate and lamotrigine, used more as anticonvulsants) as supplements in rodent chow for at least 4 weeks. All drugs attenuated novelty-induced locomotor hyperactivity of the Gria1-/- mice, especially by promoting the habituation, while none of them attenuated 2-mg/kg amphetamine-induced hyperactivity as compared to control diet. Treatment with lithium and valproate reversed the elevated exploratory activity of Gria1-/- mice. Valproate treatment also reduced struggling behaviour in tail suspension test and restored reciprocally-initiated social contacts of Gria1-/- mice to the level shown by the wild-type Gria1+/+ mice. Gria1-/- mice consumed slightly more sucrose during intermittent sucrose exposure than the wild-types, but ran similar distances on running wheels. These behaviours were not consistently affected by lithium and valproate in the Gria1-/- mice. The efficacy of various anti-manic drug treatments on novelty-induced hyperactivity suggests that the Gria1-/- mouse line can be utilized in screening for new therapeutics.
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Milica
authors.initials: M
authors.lastname: Maksimovic
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Vekovischeva
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: Teemu
authors.initials: T
authors.lastname: Aitta-aho
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland; Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore; Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore; SINAPSE, Singapore Institute for Neurotechnology, Singapore.
authors.forename: Esa R
authors.initials: ER
authors.lastname: Korpi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D005260:Female; D006948:Hyperkinesis / Q000517:prevention & control*; D008094:Lithium / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D018091:Receptors, AMPA / Q000502:physiology*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D008094:Lithium; D018091:Receptors, AMPA; D014635:Valproic Acid