Enhanced methamphetamine sensitisation in a rat model of the brain-derived neurotrophic factor Val66Met variant: Sex differences and dopamine receptor gene expression.

Sep 25, 2023

Experts: Emily J Jaehne,Hayette Semaan,Adam Grosman,Xiangjun Xu,Quenten Schwarz,Maarten van den Buuse

Brain-derived neurotrophic factor (BDNF) and the Val66Met polymorphism may play a role in the development of psychosis and schizophrenia. The aim of this study was to investigate long-term effects of methamphetamine (Meth) on psychosis-like behaviour and dopamine receptor and dopamine transporter gene expression in a novel rat model of the BDNF Val66Met polymorphism. At the end of a 7-day subchronic Meth treatment, female rats with the Met/Met genotype selectively showed locomotor hyperactivity sensitisation to the acute effect of Meth. Male rats showed tolerance to Meth irrespective of Val66Met genotype. Two weeks later, female Met/Met rats showed increased locomotor activity following both saline treatment or a low dose of Meth, a hyperactivity which was not observed in other genotypes or in males. Baseline PPI did not differ between the groups but the disruption of PPI by acute treatment with apomorphine was absent in Meth-pretreated Met/Met rats. Female Met/Met rats selectively showed down-regulation of dopamine D2 receptor gene expression in striatum. Behavioural effects of MK-801 or its locomotor sensitisation by prior Meth pretreatment were not influenced by genotype. These data suggest a selective vulnerability of female Met/Met rats to short-term and long-term effects of Meth, which could model increased vulnerability to psychosis development associated with the BDNF Val66Met polymorphism.
Copyright © 2023. Published by Elsevier Ltd.

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ABOUT THE EXPERTS

Emily J Jaehne,Hayette Semaan,Adam Grosman,Xiangjun Xu,Quenten Schwarz,Maarten van den Buuse

Emily J Jaehne

Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.

Hayette Semaan

Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.

Adam Grosman

Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.

Xiangjun Xu

Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia.

Quenten Schwarz

Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia.

Maarten van den Buuse

Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, Australia; Department of Pharmacology, University of Melbourne, Melbourne, Australia. Electronic address: m.vandenbuuse@latrobe.edu.au.