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Subchronic metabotropic glutamate 5 receptor modulation in the perinatal pcp rodent model of schizophrenia

Conference Paper


Abstract


  • Purpose: Schizophrenia is a complex neuropsychiatric disorder whereby

    symptoms present at adolescence. It is hypothesised the etiology

    of schizophrenia is due to NMDA receptor (NMDAR) hypofunction.

    Metabotropic glutamate 5 receptor (mGluR5) positive allosteric modulator

    (PAM) drugs are being investigated as a novel treatment of schizophrenia

    as an indirect manner to up-regulate NMDAR activity. We investigated

    the potential of subchronic adolescent CDPPB (an mGluR5 PAM)

    administration, to attenuate perinatal phencyclidine (PCP)-induced

    neurotransmission deficits. Methods: Male rat pups (n=6/group) were

    treated with PCP (10mg/kg) or saline on postnatal days (PN) 7, 9 and 11.

    Adolescent male rats (PN28) were administered with daily CDPPB (30mg/

    kg) injections for seven consecutive days (PN28-34) and euthanased

    on PN35. Subsequently [3H]MK-801 and [3H]MPEP radioligand binding

    were performed on brain sections corresponding to the pre-frontal cortex,

    striatum, thalamus, and hippocampus. Results: No significant differences

    were observed in NMDAR binding between any of the treatment groups

    in all brain regions examined. However mGluR5 binding density was

    significantly reduced by 31% in the ventral hippocampus of the PCP/

    CDPPB treated group compared to the saline control group (p=0.034).

    Similarly, mGluR5 binding density was significantly reduced by 49% in

    the striatum of the PCP/CDPPB treated group compared to the saline

    control group (p=0.01) and by 41% compared to the PCP/vehicle group

    (p=0.011). Conclusion: This study shows adolescent subchronic

    administration of CDPPB (30mg/kg) to have brain region specific effects

    on neurotransmission. Though we found reductions in mGluR5 binding

    density in CDPPB treated groups, this was not reflected in NMDAR binding

    density. Further investigation may prove this model a potential prevention

    tool to attenuate NMDAR hypofunction deficits.

Publication Date


  • 2013

Citation


  • Lum, J. S., Frank, E., Matosin, N., Huang, X. F. & Newell, K. A. (2013). Subchronic metabotropic glutamate 5 receptor modulation in the perinatal pcp rodent model of schizophrenia. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 173-173). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/911

Start Page


  • 173

End Page


  • 173

Place Of Publication


  • Australia

Abstract


  • Purpose: Schizophrenia is a complex neuropsychiatric disorder whereby

    symptoms present at adolescence. It is hypothesised the etiology

    of schizophrenia is due to NMDA receptor (NMDAR) hypofunction.

    Metabotropic glutamate 5 receptor (mGluR5) positive allosteric modulator

    (PAM) drugs are being investigated as a novel treatment of schizophrenia

    as an indirect manner to up-regulate NMDAR activity. We investigated

    the potential of subchronic adolescent CDPPB (an mGluR5 PAM)

    administration, to attenuate perinatal phencyclidine (PCP)-induced

    neurotransmission deficits. Methods: Male rat pups (n=6/group) were

    treated with PCP (10mg/kg) or saline on postnatal days (PN) 7, 9 and 11.

    Adolescent male rats (PN28) were administered with daily CDPPB (30mg/

    kg) injections for seven consecutive days (PN28-34) and euthanased

    on PN35. Subsequently [3H]MK-801 and [3H]MPEP radioligand binding

    were performed on brain sections corresponding to the pre-frontal cortex,

    striatum, thalamus, and hippocampus. Results: No significant differences

    were observed in NMDAR binding between any of the treatment groups

    in all brain regions examined. However mGluR5 binding density was

    significantly reduced by 31% in the ventral hippocampus of the PCP/

    CDPPB treated group compared to the saline control group (p=0.034).

    Similarly, mGluR5 binding density was significantly reduced by 49% in

    the striatum of the PCP/CDPPB treated group compared to the saline

    control group (p=0.01) and by 41% compared to the PCP/vehicle group

    (p=0.011). Conclusion: This study shows adolescent subchronic

    administration of CDPPB (30mg/kg) to have brain region specific effects

    on neurotransmission. Though we found reductions in mGluR5 binding

    density in CDPPB treated groups, this was not reflected in NMDAR binding

    density. Further investigation may prove this model a potential prevention

    tool to attenuate NMDAR hypofunction deficits.

Publication Date


  • 2013

Citation


  • Lum, J. S., Frank, E., Matosin, N., Huang, X. F. & Newell, K. A. (2013). Subchronic metabotropic glutamate 5 receptor modulation in the perinatal pcp rodent model of schizophrenia. 33rd Meeting of the Australian Neuroscience Society: Program, Abstracts & List of Registrants (pp. 173-173). Australia: ANS.

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/911

Start Page


  • 173

End Page


  • 173

Place Of Publication


  • Australia