Title

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

RIS ID

80295

Publication Details

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, ANS, Australia, pp. 173-173.

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.

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