Rearing animals in isolation from weaning has previously been shown to produce alterations in neurochemistry and behaviour and to influence the effect of psychotomimetics on behaviour (Lapiz et al, 2003). Previous work in our laboratory demonstrated a deficiency in reversal learning following sub-chronic PCP administration, an effect that may correlate to a loss in GABAergic interneurons (Reynolds et al, 2004). Recent human post-mortem studies in schizophrenia have shown a loss in parvalbumin-immunoreactive (parvalbumin-IR) GABAergic interneuron cell density in both frontal cortical and hippocampal regions of the brain (Reynolds & Beasley, 2001), areas that are increasingly being associated with cognitive function. Thus, the present study aims to investigate the influence of isolation rearing on GABAergic interneuron cell density and size, using parvalbumin-IR as a marker for GABAergic interneurons (Benes & Berretta, 2001), within the frontal cortex (FC) and hippocampus in both socials and isolates.

Female rats (hooded-Lister, ± 250g) were isolated at weaning and maintained under standard laboratory conditions for a period of 12 weeks (n=12 per housing group). Following the isolation period, animal brains were removed and analysed using immunohistochemical techniques to determine the size and density of parvalbumin-IR interneurons. Differences between social and isolated animals were statistically analysed by a one-way ANOVA, with a post hoc Dunnett’s test. Data are expressed as mean ± s.e.m.

Isolated animals, when compared to social animals, showed a significant increase in parvalbumin-IR cell density in cingulate cortex (CG1) region [32.2±2.9, socials and 47.5±3.1, isolates, P<0.01] and motor (M2) region of the frontal cortex [54.3±2.4 socials compared to 76.2±5.2 isolates, P<0.01], in addition to an increase in cell size within the M2 region of the frontal cortex [52.6±5.2 socials compared to 85.1±5.6 isolates, P<0.01]. Within the hippocampus, isolates demonstrated a significant increase in parvalbumin-IR interneuron cell density within the hippocampal dentate gyrus (DG) region [10.1±0.4 socials and 43.2±1.2 isolates, P<0.001], in addition to a significant decrease in cell size [121.9±4.6 compared to 73.1±15.6, P<0.01], when compared to social animals. In contrast to the latter effect, isolated animals, when compared to socials, demonstrated significant decreases in cell density in both the CA3/2 [22.4±1.0 compared to 16.2±1.5, p<0.01] and CA1 [27.9±2.7 compared to16.7±2.2, P<0.01] regions of the hippocampus. In addition, isolated animals expressed a significantly lower CA1 cell size when compared to socially reared animals [157.8±5.2 compared to 107.0±2.7, P<0.05]. These preliminary data suggest that significantly differential parvalbumin-IR density is expressed between social and isolated rats. Such effects that may underlie some of the behavioural alterations observed following social isolation.

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