Social isolation stress significantly enhanced the disruption of prepulse inhibition in mice repeatedly treated with methamphetamine

Hongmei Dai, Hirotomo Okuda, Kentaro Iwabuchi, Eiko Sakurai, Zhong Chen, Motohisa Kato, Kazuie Iinuma, Kazuhiko Yanai

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Repeated administration of methamphetamine (METH) causes reverse tolerance or behavioral sensitization in mice. However, the effects of social isolation stress on the METH-caused reverse tolerance have not been studied until now. The aim of this study was to investigate the effects of social isolation stress on METH-caused reverse tolerance by examining the prepulse inhibition of startle response (PPI). PPI was tested in socially isolated and grouped mice after repeated METH injections. Locomotor activity and PPI were also examined just after a four-week isolation rearing period as a control experiment. After completing behavioral experiments, the mice were sacrificed, and the contents of monoamines, including histamine in the brain, were measured. Social isolation stress significantly lowered the locomotion and disrupted PPI. Repeated injections of METH enhanced the effects of social isolation on PPI. The content of dopamine and histamine significantly increased in the cortex, and the turnover rate of dopamine decreased significantly. These findings demonstrate that social isolation stress significantly enhances METH-induced behavioral sensitization and that the altered histaminergic neuron system might play an important role in METH-induced behavioral sensitization in addition to dopaminergic and serotoninergic neurotransmission. Our data suggest that social isolation is involved in the development of METH-induced psychosis, schizophrenia, and other related psychiatric disorders.

Original languageEnglish
Pages (from-to)257-266
Number of pages10
JournalAnnals of the New York Academy of Sciences
Publication statusPublished - 2004


  • Behavioral sensitization
  • Dopamine
  • Histamine
  • Locomotor activity
  • Methamphetamine
  • Prepulse inhibition
  • Social isolation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


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