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

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

doi:10.1016/j.neuropharm.2023.109719

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

Neuropharmacology. 2023 Dec 1:240:109719. doi: 10.1016/j.neuropharm.2023.109719. Epub 2023 Sep 22.

Authors

Emily J Jaehne¹, Hayette Semaan¹, Adam Grosman¹, Xiangjun Xu², Quenten Schwarz², Maarten van den Buuse³

Affiliations

¹ Department of Psychology and Counselling, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
² Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, Australia.
³ 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.

PMID: 37742717
DOI: 10.1016/j.neuropharm.2023.109719

Abstract

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.

Keywords: Brain-derived neurotrophic factor; Dopamine; Methamphetamine; Psychosis; Schizophrenia; Val66Met.