Modelling the cognitive and neuropathological features of schizophrenia with phencyclidine.
Here, Reynolds and Neill describe the studies that preceded and followed publication of this paper, which reported a deficit in parvalbumin (PV), a calcium-binding protein found in GABA interneurons known to be reduced in schizophrenia patients, in conjunction with a deficit in reversal learning in an animal model for schizophrenia. This publication resulted from common research interests: Reynolds in the neurotransmitter pathology of schizophrenia, and Neill in developing animal models for schizophrenia symptomatology. The animal model, using a sub-chronic dosing regimen (sc) with the non-competitive NMDA receptor antagonist PCP (phencyclidine), evolved from previous work in rats (for PCP) and primates (for cognition). The hypothesis of a PV deficit came from emerging evidence for a GABAergic dysfunction in schizophrenia, in particular a deficit in PV-containing GABA interneurons. Since this original publication, a PV deficit has been identified in other animal models for schizophrenia, and the PV field has expanded considerably. This includes mechanistic work attempting to identify the link between oxidative stress and GABAergic dysfunction using this scPCP model, and assessment of the potential of the PV neuron as a target for new antipsychotic drugs. The latter has included development of a molecule targeting KV3.1 channels located on PV-containing GABA interneurons which can restore both PV expression and cognitive deficits in the scPCP model.
Sheffield Hallam University, Biomolecular Sciences Research Centre, Sheffield, UK.
Gavin P
GP
Reynolds
Manchester Pharmacy School, University of Manchester, Manchester, UK joanna.neill@manchester.ac.uk.
Joanna C
JC
Neill
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D006801:Humans; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D010320:Parvalbumins / Q000494:pharmacology / Q000627:therapeutic use; D010622:Phencyclidine / Q000494:pharmacology* / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D014150:Antipsychotic Agents; D010320:Parvalbumins; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid; D010622:Phencyclidine
GABA; PCP; Schizophrenia; cognition; parvalbumin; rat