title: Disruptions of sensorimotor gating, cytokines, glycemia, monoamines, and genes in both sexes of rats reared in social isolation can be ameliorated by oral chronic quetiapine administration.
abstract: The pathogenesis of schizophrenia in patients with metabolic abnormalities remains unclear. Our previous study demonstrated that isolation rearing (IR) induced longitudinal concomitant changes of pro-inflammatory cytokine (pro-CK) levels and metabolic abnormalities with a developmental origin. However, the general consensus, believes that these abnormalities are caused by antipsychotic treatment in schizophrenic patients. The IR paradigm presents with face, construct, and predictive validity for schizophrenia. Therefore, we employed IR rats of both sexes to examine whether chronic quetiapine (QTP, a second-generation antipsychotic medication) treatment induces disruptions of metabolism (body weight, blood pressure, and the glycemic and lipid profiles) or cytokines [interleukin (IL)-1 beta, IL-6, IL-10, interferon-gamma, and tumor necrosis factor (TNF)-alpha], and further, whether it reverses deficits of behaviors [locomotor activity and prepulse inhibition (PPI)] and the expression of monoamines (dopamine and serotonin) and related genes (Htr1a, Htr2a, Htr3a, Drd1a, and Gabbr2). IR induced higher levels of pro-CK, dysglycemia, blood pressure, locomotor activity, and impaired PPI, simultaneously destabilizing cortico-striatal monoamines and relevant genes in both sexes, while QTP demonstrated dose-dependent reversal of these changes, suggesting that QTP might reduce the pro-CKs to regulate these abnormalities. Our data implied that antipsychotics may not be the solitary factor causing metabolic problems in schizophrenia and suggested that inflammatory changes may play a vital role in the developmental pathophysiology of schizophrenia and related metabolic abnormalities.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Ko
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei 11490, Taiwan; Department of Psychiatry, Tri-Service General Hospital, Taipei 11490, Taiwan. Electronic address: yiaping@ms75.hinet.net.
authors.forename: Yia-Ping
authors.initials: YP
authors.lastname: Liu
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000378:metabolism; D065808:Prepulse Inhibition / Q000187:drug effects*; D000069348:Quetiapine Fumarate / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics; D018080:Receptors, GABA-B / Q000235:genetics; D011985:Receptors, Serotonin / Q000235:genetics; D012701:Serotonin / Q000378:metabolism; D012934:Social Isolation; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D016207:Cytokines; C116566:Gabbr2 protein, rat; D017447:Receptors, Dopamine D1; D018080:Receptors, GABA-B; D011985:Receptors, Serotonin; D000069348:Quetiapine Fumarate; D012701:Serotonin; D004298:Dopamine
keywords: Cytokines; Development; Isolation rearing; Metabolic abnormalities; Quetiapine; Schizophrenia