Abstract
Reelin has been implicated in the development of schizophrenia but the mechanisms involved in this interaction remain unclear. Chronic methamphetamine (Meth) use may cause dopaminergic sensitisation and psychosis and has been proposed to affect brain dopamine systems similarly to changes seen in schizophrenia. We compared the long-term effect of chronic Meth treatment between heterozygous reelin mice (HRM) and wildtype controls (WT) with the aim of better understanding the role of reelin in schizophrenia. Meth pretreatment induced sensitisation to the effect of an acute Meth challenge on locomotor activity, but it had no effect on baseline PPI or sociability and social preference. In all behavioural models, HRM did not significantly differ from WT at baseline, except spontaneous exploratory locomotor activity which was higher in HRM than WT, and sociability which was enhanced in HRM. Locomotor hyperactivity sensitisation was not significantly different between HRM and WT. Chronic Meth treatment reduced spontaneous locomotor activity to the level of WT. No deficits in PPI or social behaviour were induced by chronic Meth pretreatment in either strain. In conclusion, these data do not support a role of reelin in schizophrenia, at least not in HRM and in the methamphetamine sensitisation model.
Highlights
Reelin is an important extracellular protein involved in neuronal migration and brain layer formation during prenatal neurodevelopment
Body weights in Meth-pretreated mice tended to be higher than those in saline controls, this difference did not reach statistical significance (p = 0.065). These data show that Meth pretreatment did not result in reduced body weight gain heterozygous reelin mice (HRM) gained weight slightly slower than wildtype controls (WT) mice
The aim of this study was to investigate the effects of chronic Meth on behaviour of HRM and WT mice, with the ultimate aim to better understand the possible role of reelin in schizophrenia
Summary
Reelin is an important extracellular protein involved in neuronal migration and brain layer formation during prenatal neurodevelopment In adulthood it plays a complex role in synaptic plasticity by altering dendritic spine morphology, regulating N-methyl-D-aspartate (NMDA) glutamate receptor function and influencing neurotransmitter synthesis [1,2]. Reelin supplementation in the form of a single ventricular injection has been shown to recover schizophrenia-like deficits in mice [4]. These findings have led to the suggestion that this protein may play an important role in schizophrenia vulnerability [1,3,5]. It remains unclear through which neurotransmitter mechanisms reelin plays a role in schizophrenia
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