Peripheral Neuregulin-1 administration suppresses PCP-induced hyperlocomotion in adult mice

Annual meeting Biological Psychiatry Australia 2012, Melbourne (Australia)

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 patients with schizophrenia. 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 intraperitoneal (ip) application of Neuregulin-1, mutations of which have been implicated in schizophrenia pathology, to suppress PCP-induced hyperlocomotion.

Method: Following habituation in an open field chamber, saline or PCP (3 mg/kg, ip) were administered to adult C57Bl/6 mice (n=8 per group) with or without simultaneous ip application of either 5 µg/kg, 25 µg/kg or 50 µg/kg human recombinant Neuregulin-1 (NRG1β1 EGF Domain). Following the injections locomotor activity was measured for 30 minutes.

Results: The PCP application induced significant hyperlocomotion as frequently shown before. IP application of NRG1β1 alone did not change locomotor activity compared to controls. When co-administered, however, 25 µg/kg NRG1β1 significantly reduced PCP-induced hyperlocomotion. NRG1β1 acted in a U-shaped dose dependent manner with hyperlocomotion being suppressed by treatment with 25 µg/kg but not 5 µg/kg or 50 µg/kg NRG1β1.

Conclusion: These results indicate that application of NRG1β1 might be relevant for the treatment of schizophrenia. In ongoing experiments weare 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 BPA Poster

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