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The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice:
Camilla Hume1, Shelley Massey1, Maarten van den Buuse1
1School of Psychology and Public Health, La Trobe University, Melbourne, VIC 3086, Australia.
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.
Insights
This study found that reelin deficiency did not alter behavioral responses to chronic methamphetamine exposure in mice. These findings do not support a role for reelin in schizophrenia pathogenesis using this model.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Reelin is implicated in schizophrenia, but its precise role is unclear.
- Chronic methamphetamine (Meth) use can induce psychosis and affect dopamine systems, mirroring some schizophrenia-related changes.
- Understanding reelin's function in Meth-induced behavioral changes may elucidate its role in schizophrenia.
Purpose of the Study:
- To investigate the long-term effects of chronic Meth treatment on heterozygous reelin mice (HRM) compared to wildtype (WT) controls.
- To assess the role of reelin in Meth-induced behavioral sensitization and social behaviors.
Main Methods:
- Chronic Methamphetamine (Meth) administration to HRM and WT mice.
- Assessment of locomotor activity, prepulse inhibition (PPI), and social behavior (sociability and social preference).
- Comparison of behavioral responses between HRM and WT mice before and after chronic Meth treatment.
Main Results:
- HRM exhibited higher baseline exploratory locomotor activity and enhanced sociability compared to WT.
- Chronic Meth treatment induced locomotor activity sensitization in both HRM and WT mice, with no significant difference between genotypes.
- Chronic Meth treatment reduced spontaneous locomotor activity in both groups and did not induce deficits in PPI or social behavior.
Conclusions:
- The study's findings do not support a significant role for reelin in the observed behavioral effects of chronic Meth exposure.
- Reelin deficiency in HRM did not alter the development of Meth-induced locomotor sensitization or social behavior deficits.
- The results suggest reelin may not be a critical factor in the methamphetamine sensitization model of psychosis relevant to schizophrenia.
