title: Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.
abstract: Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia; Translational OCD Laboratory, Department of Psychiatry, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Manning
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, Australia. Electronic address: m.vandenbuuse@latrobe.edu.au.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Buuse
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D005260:Female; D006579:Heterozygote; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012727:Sex Characteristics; D012920:Social Behavior Disorders / Q000139:chemically induced* / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D008694:Methamphetamine
keywords: BDNF; Methamphetamine; Psychosis; Schizophrenia; Social behaviour