title: An animal model of emotional blunting in schizophrenia.
abstract: Schizophrenia is often associated with emotional blunting--the diminished ability to respond to emotionally salient stimuli--particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed.
authors.affiliation: Graduate School of Behavioral and Cognitive Neuroscience, Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. charmspiet@hotmail.com
authors.forename: Charmaine Y
authors.initials: CY
authors.lastname: Pietersen
authors.forename: Fokko J
authors.initials: FJ
authors.lastname: Bosker
authors.forename: Janine
authors.initials: J
authors.lastname: Doorduin
authors.forename: Minke E
authors.initials: ME
authors.lastname: Jongsma
authors.forename: Folkert
authors.initials: F
authors.lastname: Postema
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Haas
authors.forename: Michael P
authors.initials: MP
authors.lastname: Johnson
authors.forename: Tineke
authors.initials: T
authors.lastname: Koch
authors.forename: Tony
authors.initials: T
authors.lastname: Vladusich
authors.forename: Johan A
authors.initials: JA
authors.lastname: den Boer
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003214:Conditioning, Classical; D004298:Dopamine / Q000378:metabolism; D004644:Emotions; D005239:Fear; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012565:Schizophrenic Psychology
chemical_list: D018698:Glutamic Acid; D004298:Dopamine