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The effect of ketamine on the consolidation and extinction of contextual fear memory

Clifton, Nicholas, Thomas, Kerrie and Hall, Jeremy 2018. The effect of ketamine on the consolidation and extinction of contextual fear memory. Journal of Psychopharmacology 32 (2) , pp. 156-162. 10.1177/0269881117748903

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Abstract

Ketamine, principally an antagonist of N-methyl-ᴅ-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-ᴅ-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia. To further investigate the impact of ketamine on associative fear learning, we studied the effects of pre- and post-training ketamine on the consolidation and extinction of contextual fear memory in rats. Administration of 25 mg/kg ketamine prior to fear conditioning did not affect consolidation when potentially confounding effects of state dependency were controlled for. Pre-training ketamine (25 mg/kg) impaired the extinction of the conditioned fear response, which was mirrored with the use of a lower dose (8 mg/kg). Post-training ketamine (25 mg/kg) had no effect on the consolidation or extinction of conditioned fear. These observations implicate processes relating to the extinction of contextual fear memory in the manifestation of ketamine-induced phenotypes, and are consistent with existing hypotheses surrounding abnormal associative learning in schizophrenia

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: SAGE Publications
ISSN: 0269-8811,
Date of First Compliant Deposit: 7 December 2017
Date of Acceptance: 23 November 2017
Last Modified: 28 Jul 2019 21:22
URI: http://orca-mwe.cf.ac.uk/id/eprint/107409

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