Nov 30, 2013

Acute and chronic effects of NMDA receptor antagonists in rodents, relevance to negative symptoms of schizophrenia: a translational link to humans

European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology
Joanna C NeillDominic M Dwyer

Abstract

Negative symptoms of schizophrenia remain an unmet clinical need as they are common, persistent, respond poorly to existing treatments and lead to disability. Blunted affect, alogia, asociality, anhedonia and avolition are regarded as key negative symptoms despite DSM-IV-TR specifying a more limited range. The key to development of improved therapies is improved animal models that mimic the human condition in terms of behaviour and pathology and that predict efficacy of novel treatments in patients. Accumulating evidence shows that NMDA receptor (NMDAR) antagonists mimic cognitive deficits of relevance to schizophrenia in animals, along with associated pathological changes. This review examines evidence for the ability of NMDAR antagonists to mimic anhedonia and asociality, two negative symptoms of schizophrenia, in animals. The use of various species, paradigms and treatment regimens are reviewed. We conclude that sub-chronic treatment with NMDAR antagonists, typically PCP, induces social withdrawal in animals but not anhedonia. NMDAR antagonists have further effects in paradigms such as motivational salience that may be useful for mimicking other aspects of negative symptoms but these require further development. Sub-chronic ...Continue Reading

Mentioned in this Paper

Short Stature, Auditory Canal Atresia, Mandibular Hypoplasia, Skeletal Abnormalities
Drug Development
Social Anhedonia
Adrenal Cortex Diseases
Assay OF Haloperidol
Prefrontal Cortex
Schizophrenia
MAT1A gene
SLC6A9 gene
Clozapine

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