Title

Perinatal PCP treatment alters the developmental expression of prefrontal and hippocampal muscarinic receptors

RIS ID

25056

Publication Details

du Bois, T., Newell, K., Han, M., Deng, C. & Huang, X. (2009). Perinatal PCP treatment alters the developmental expression of prefrontal and hippocampal muscarinic receptors. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33 (1), 37-40.

Abstract

Perinatal phencyclidine (PCP) treatment has been used to model brain pathological processes that may be present in schizophrenia such as increased apoptosis during early brain development, and long-term alterations in expression of parvalbumin-containing interneurons and glutamatergic N-methyl-d-aspartate (NMDA) receptors. We report that this treatment also affects receptor expression of another excitatory neurotransmitter receptor, the muscarinic receptor. Female rat pups received injections of the NMDA receptor antagonist PCP (10 mg/kg, s.c.) or saline on postnatal days (PN)7, 9 and 11. [3H]Pirenzepine binding to M1/4 receptors was examined at four time-points (PN12, 18, 32 and 96) following treatment cessation. Significant effects of treatment on [3H]pirenzepine binding were evident immediately after treatment cessation with a decrease in PCP-treated rats at PN12 in the prefrontal cortex (− 24%, p < 0.05) and hippocampus (− 19%, p < 0.05). After this initial decrease, binding subsequently increased to 47% above control levels in the prefrontal cortex of adolescent animals, which remained elevated in adulthood (+ 10%, p < 0.05), while in the hippocampus there was a trend towards increased binding in adolescent animals and no change thereafter. This work adds to findings demonstrating that perinatal PCP exposure leads to long-term imbalance of excitatory and inhibitory neurotransmitter systems, supporting its relevance as a developmental model of schizophrenia pathology. Alterations in muscarinic receptor expression may contribute specifically to the cognitive impairments reported to occur after perinatal NMDA receptor antagonist treatment.

Grant Number

NHMRC/573426

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