title: Dopaminergic activity and behaviour in SOCS2 transgenic mice: Revealing a potential drug target for schizophrenia.
abstract: Alterations in immune function have been implicated in the aetiopathogenesis of schizophrenia. Specifically, the induction of inflammatory cytokines, which are important immunological factors in infection or inflammation, may be critical factors altering the normal course of brain development and increasing schizophrenia risk. Suppressor of cytokine signalling 2 (SOCS2) can negatively regulate the signalling of cytokines. The present study aimed to determine the behavioural phenotype of transgenic mice over-expressing SOCS2 (SOCS2 Tg) in paradigms of relevance to schizophrenia. Both male and female SOCS2 Tg mice displayed reduced locomotor hyperactivity after the administration of the dopamine releaser, amphetamine, compared to wildtype controls (WT). However, only male SOCS2 Tg mice showed enhanced prepulse inhibition compared to WT. Dopamine D2 receptors mRNA expression was reduced and dopamine transporter mRNA expression was increased in the nucleus accumbens of female, but not male, SOCS2 Tg mice, compared to WT. The role of hyperdopaminergia has long been implicated in the aetiology of schizophrenia. This study shows that over-expression of SOCS2 reduces the psychostimulant effects of amphetamine, enhances PPI, and alters mesolimbic dopaminergic activity. SOCS2 may provide a novel target in the development of treatments for schizophrenia.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia.
authors.forename: Udani
authors.initials: U
authors.lastname: Ratnayake
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Australia.
authors.forename: Harleen S
authors.initials: HS
authors.lastname: Basrai
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Australia.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Turnley
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia; Department of Pharmacology and Therapeutics, University of Melbourne, Australia; School of Psychological Science, La Trobe University, Melbourne, Australia. Electronic address: m.vandenbuuse@latrobe.edu.au.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D008124:Locomotion / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D065808:Prepulse Inhibition / Q000187:drug effects / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D004298:Dopamine
keywords: Dopamine; Locomotor hyperactivity; Nucleus accumbens; Prepulse inhibition; SOCS2; Schizophrenia