Isolation rearing impaired sensorimotor gating but increased pro-inflammatory cytokines and disrupted metabolic parameters in both sexes of rats

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

“…In the present study, we first confirmed the results of our previous study (Ko and Liu, 2015) regarding whether IR rats have metabolic abnormalities concomitant with changed pro-CK levels around puberty. Subsequently, we examined whether QTP is beneficial for the metabolic and cytokine abnormalities in IR rats of both sexes.…”

“…However, widespread findings showed that the disorder itself has a predisposing or primary role in metabolic abnormalities (Ryan et al, 2003;Mitchell et al, 2013b), as evidenced by the fact that drug-naive patients/first-episode schizophrenia is prone to glycemic abnormalities (Cohn et al, 2006;Fernandez-Egea et al, 2009;Nielsen et al, 2010). These human studies are in line with our previous pre-clinical findings, in which increased insulin resistance, decreased insulin sensitivity, and high blood pressure concomitant with aberrant cytokine levels were observed in a rat model of isolation rearing (IR), a developmental paradigm in modeling schizophrenia (Ko and Liu, 2015).…”

“…Our previous study (Ko and Liu, 2015) found that IR for 4 weeks (7-week-old animals) induces PPI deficits, hyperlocomotion activity, metabolic abnormalities, and aberrant cytokines. Afterwards, both sexes of rats were orally treated by gastric gavages with saline or quetiapine (kindly provided by the local representative agency Ko & Liu 9 of AstraZeneca, the Chi-Fu Trading Co., Ltd., Taipei, Taiwan) once per day for 28 days.…”

“…The IR paradigm is a neurodevelopmental model of early life chronic stress in modeling schizophrenia, including the involvement of oxidative stress and inflammation (Möller et al, 2013a, b), for example, altered expressions of c-fos, anti-oxidative enzymes, and levels of certain cytokines (Muchimapura et al, 2002;Möller et al, 2011Möller et al, , 2013aKo and Liu, 2015). Oxidative stress and inflammation also evoke disruptions of dopamine (DA) and serotonin (5-HT), and the expression of schizophrenic genes was observed in the prefrontal cortex (PFC), hippocampus, and striatum of IR rats (Brenes and Fornaguera, 2009;Sun et al, 2012;Kishi et al, 2014;Möller et al, 2013a;Selvaraj et al, 2014), resulting in behavioral deficits, particularly that the IR rats may develop an impairment of prepulse inhibition which refers to the dysfunction of sensorimotor gating in schizophrenia and schizophrenia spectrum patients (Fone and Porkess, 2008;Möller et al, 2013b).…”

Social Isolation Rearing Induces Neuropsychiatric Diseases: Updated Overview

“…The antagonist of cannabinoids has been shown to be effective for the long-lasting treatment of psychotic symptoms [67]. Disturbance of the immune system after social isolation rearing points toward therapy that is directed at immune system abnormalities [68, 69]. …”