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.