PCP-induced hyperlocomotion reduced by intracerebral Neuregulin-1 application in adult mice

Biannual meeting of the Federation of European Neuroscience Societies (FENS) 2012, Barcelona (Spain)

Martin Engel, Xu-Feng Huang, Elisabeth Frank

Background: Phencyclidine (PCP) can produce schizophrenia-like symptoms in healthy humans and exacerbate positive and negative symptoms in schizophrenia patients. Acute PCP administration to animals has been shown to induce schizophrenia-relevant characteristics, including hyperlocomotion. Antagonising the PCP-induced behavioural changes has been previously used as an indicator for the antipsychotic potential of a compound. This study therefore explores the potential of an intraventricular (icv) application of Neuregulin-1, which has been implicated in the schizophrenia pathology, to suppress PCP-induced hyperlocomotion.

Method: Following habituation in an open field chamber, saline or PCP (3 mg/kg, intraperitoneal) were administered to adult C57Bl/6 mice (n=8 per group) with or without simultaneous icv application of either 30 ng/kg or 3 ng/kg human recombinant Neuregulin-1 (NRG1β1 EGF Domain). Locomotor activity was measured following the injections for 30 minutes.

Results: The PCP application induced significant hyperlocomotion as frequently shown before. ICV application of 30 ng/kg NRG1β1 alone did not change locomotor activity compared to controls. When co-administered, however, 30 ng/kg NRG1β1 significantly reduced PCP-induced hyperlocomotion. NRG1β1 acted in a dose dependant manner with hyperlocomotion being suppressed by treatment with 30 ng/kg but not 3 ng/kg NRG1β1.

Conclusion: These results indicate that Neuregulin-1 might be relevant for the treatment of schizophrenia. In ongoing experiments we are addressing the effect of Neuregulin-1 on schizophrenia-related neurotransmission and cell survival to examine the underlying mechanisms and to further explore its antipsychotic potential.

Download poster: Engel et al 2012 FENS Poster

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