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BDNF-Deficient Mice Show Reduced Psychosis-Related Behaviors Following Chronic Methamphetamine
Elizabeth E Manning1, Adam L Halberstadt1, Maarten van den Buuse2
1Florey Institute of Neuroscience and Mental Health Research, University of Melbourne, Victoria, Australia (Drs Manning and van den Buuse); Translational OCD Laboratory, Department of Psychiatry, University of Pittsburgh, PA (Dr Manning); Department of Psychiatry, University of California San Diego, La Jolla, CA (Dr Halberstadt); School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia (Dr van den Buuse).
Background:
One of the most devastating consequences of methamphetamine abuse is increased risk of psychosis. Brain-derived neurotrophic factor has been implicated in both psychosis and neuronal responses to methamphetamine. We therefore examined persistent psychosis-like behavioral effects of methamphetamine in brain-derived neurotrophic factor heterozygous mice.
Methods:
Mice were chronically treated with methamphetamine from 6 to 9 weeks of age, and locomotor hyperactivity to an acute D-amphetamine challenge was tested in photocell cages after a 2-week withdrawal period.
Results:
Methamphetamine-treated wild-type mice, but not brain-derived neurotrophic factor heterozygous mice, showed locomotor sensitization to acute 3mg/kg D-amphetamine. Qualitative analysis of exploration revealed tolerance to D-amphetamine effects on entropy in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice, but not wild-type mice.
Conclusions:
Chronic methamphetamine exposure induces contrasting profiles of behavioral changes in wild-type and brain-derived neurotrophic factor heterozygous mice, with attenuation of behaviors relevant to psychosis in methamphetamine-treated brain-derived neurotrophic factor heterozygous mice. This suggests that brain-derived neurotrophic factor signalling changes may contribute to development of psychosis in methamphetamine users.
