The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats

Abstract

Similar to its clinical profile, risperidone only partially reverses the schizophrenic symptomology; since it reversed some, but not all, of the learning and memory deficits induced by post-weaning isolation, the isolation rearing model may be useful to predict antipsychotic activity of novel therapeutic agents.

Down-Regulation of Hippocampal Genes Regulating Dopaminergic, GABAergic, and Glutamatergic Function Following Combined Neonatal Phencyclidine and Post-Weaning Social Isolation of Rats as a Neurodevelopmental Model for Schizophrenia

“…Both isolation-rearing (Jones et al, 2011; Watson et al, 2012; McIntosh et al, 2013) and repeated PCP-injection to adult rats (McKibben et al, 2010; Grayson et al, 2015) impair NOR, as does combined PCP-SI (Gaskin et al, 2014; Watson et al, 2016), consistent with findings in this study. Lamotrigine at the low (10mg/kg i.p.)…”

“…Despite there being no overall significant effect of lamotrigine on locomotor activity [F (2,31) = 2.985, p = 0.065], there was a significant housing x drug interaction [F (1,31) = 5.501, p = 0.025] over the 60min session, reflecting a reduction in activity due to lamotrigine treatment in the isolation-reared animals only (Figure 1A). Furthermore, two-way ANOVA of total activity during the first 30min (where activity differences were most marked, as often found in isolation studies; Bianchi et al, 2006; Fabricius et al, 2010; McIntosh et al, 2013) revealed a significant rearing x drug interaction [F (1,32) = 6.719, p = 0.014], but no main effect of either rearing condition or drug treatment alone (Figure 1B). Of note, post hoc analysis confirmed there was a significant increase ( p < 0.05) in locomotion in PCP-SI-V compared to control V-GH-V rats, which was significantly reduced ( p < 0.05) by the highest dose of lamotrigine (PCP-SI-L15) compared to that in PCP-SI-V rats.…”

“…In order to assess the exploratory response to a novel arena, which is recognized as a valid marker for positive symptoms sensitive to antipsychotic treatment (Fabricius et al, 2010; Jones et al, 2011; McIntosh et al, 2013), open field locomotor exploratory activity (LMA) was recorded in infrared activity chambers (clear Perspex boxes 39 x 23.5 x 24.5cm). Rats were assigned individual chambers crossed by infrared beams (Photobeam Activity System, San Diego Instruments) to measure horizontal ambulatory movements as number of beams broken in 10min bins for 1h (Bianchi et al, 2006; Jones et al, 2011).…”

A novel escapable social interaction test reveals that social behavior and mPFC activation during an escapable social encounter are altered by post-weaning social isolation and are dependent on the aggressiveness of the stimulus rat

“…al. study, from P19 to P73, compared to P28 to P52 in the current study, and longer lasting isolation has been accompanied by learning deficits [25] and amotivation for social interaction [57]. Second, the study of Hermes et al used female rats, which could indicate sex differences in the effects of isolation rearing on mPFC PSD-95.…”

“…The SA is limited in this regard as the stimulus animal is confined to a cage, and while CPP allows for behavioral monitoring during training, the later testing phase prohibits harvesting tissue within relevant time frames to examine immediate early gene expression in response to the social behavior, which occurs within a timeframe between 1 and 2 hours [24]. Additionally, the use of “escapable” social interaction may provide a direct measure of social interaction-seeking behavior reflective of motivational drive in the absence of a learned association with a specific environment as in CPP, which may be confounding in ISO rats as PSI induces learning deficits [25]. Furthermore, the ESIT allows for the manipulation of the behavioral phenotype of the stimulus rat.…”