title: Chronic ketamine produces altered distribution of parvalbumin-positive cells in the hippocampus of adult rats.
abstract: The underlying mechanisms of schizophrenia pathogenesis are not well understood. Increasing evidence supports the glutamatergic hypothesis that posits a hypofunction of the N-methyl D-aspartate (NMDA) receptor on specific gamma amino-butyric acid (GABA)-ergic neurons may be responsible for the disorder. Alterations in the GABAergic system have been observed in schizophrenia, most notably a change in the expression of parvalbumin (PV) in the cortex and hippocampus. Several reports also suggest abnormal neuronal migration may play a role in the etiology of schizophrenia. The current study examined the positioning and distribution of PV-positive cells in the hippocampus following chronic treatment with the NMDA receptor antagonist ketamine. A robust increase was found in the number of PV-positive interneurons located outside the stratum oriens (SO), the layer where most of these cells are normally localized, as well as an overall numerical increase in CA3 PV cells. These results suggest ketamine leads to an abnormal distribution of PV-positive cells, which may be indicative of aberrant migratory activity and possibly related to the Morris water maze deficits observed. These findings may also be relevant to alterations observed in schizophrenia populations.
authors.affiliation: Department of Psychology, University of Nevada Las Vegas, Las Vegas NV 89154, United States.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Sabbagh
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Murtishaw
authors.forename: Monica M
authors.initials: MM
authors.lastname: Bolton
authors.forename: Chelcie F
authors.initials: CF
authors.lastname: Heaney
authors.forename: Michael
authors.initials: M
authors.lastname: Langhardt
authors.forename: Jefferson W
authors.initials: JW
authors.lastname: Kinney
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D010320:Parvalbumins; D007649:Ketamine
keywords: Hippocampus; Ketamine; Parvalbumin; Schizophrenia