PMID- 25591475
OWN - NLM
STAT- MEDLINE
DCOM- 20150921
LR  - 20150209
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 282
DP  - 2015 Apr 1
TI  - Ketamine administration during the second postnatal week induces enduring 
      schizophrenia-like behavioral symptoms and reduces parvalbumin expression in the 
      medial prefrontal cortex of adult mice.
PG  - 165-75
LID - S0166-4328(15)00014-5 [pii]
LID - 10.1016/j.bbr.2015.01.010 [doi]
AB  - Dysfunctions in the GABAergic system are considered a core feature of 
      schizophrenia. Pharmacological blockade of NMDA receptors (NMDAR), or their 
      genetic ablation in parvalbumin (PV)-expressing GABAergic interneurons can induce 
      schizophrenia-like behavior in animals. NMDAR-mediated currents shape the 
      maturation of GABAergic interneurons during a critical period of development, 
      making transient blockade of NMDARs during this period an attractive model for 
      the developmental changes that occur in the course of schizophrenia's 
      pathophysiology. Here, we examined whether developmental administration of the 
      non-competitive NMDAR antagonist ketamine results in persistent deficits in 
      PFC-dependent behaviors in adult animals. Mice received injections of ketamine 
      (30mg/kg) on postnatal days (PND) 7, 9 and 11, and then tested on a battery of 
      behavioral experiments aimed to mimic major symptoms of schizophrenia in 
      adulthood (between PND 90 and 120). Ketamine treatment reduced the number of 
      cells that expressed PV in the PFC by  approximately 60% as previously described. Ketamine 
      affected performance in an attentional set-shifting task, impairing the ability 
      of the animals to perform an extradimensional shift to acquire a new strategy. 
      Ketamine-treated animals showed deficits in latent inhibition, novel-object 
      recognition and social novelty detection compared to their SAL-treated 
      littermates. These deficits were not a result of generalized anxiety, as both 
      groups performed comparably on an elevated plus maze. Ketamine treatment did not 
      cause changes in amphetamine-induced hyperlocomotion that are often taken as 
      measures for the positive-like symptoms of the disorder. Thus, ketamine 
      administration during development appears to be a useful model for inducing 
      cognitive and negative symptoms of schizophrenia.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Jeevakumar, Vivek
AU  - Jeevakumar V
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Driskill, Christopher
AU  - Driskill C
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Paine, Alyssa
AU  - Paine A
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Sobhanian, Millad
AU  - Sobhanian M
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Vakil, Haris
AU  - Vakil H
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Morris, Brett
AU  - Morris B
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Ramos, Jeremiah
AU  - Ramos J
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA.
FAU - Kroener, Sven
AU  - Kroener S
AD  - School of Behavioral and Brain Sciences, The University of Texas at Dallas, 
      Richardson, TX 75080, USA. Electronic address: kroener@utdallas.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150113
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Parvalbumins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Behavioral Symptoms/chemically induced/*psychology
MH  - Disease Models, Animal
MH  - Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology
MH  - Ketamine/administration & dosage/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Parvalbumins/*metabolism
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
MH  - Schizophrenia/chemically induced/*metabolism
OTO - NOTNLM
OT  - Ketamine
OT  - NMDAR
OT  - Parvalbumin
OT  - Perinatal
OT  - Prefrontal cortex
OT  - Schizophrenia
EDAT- 2015/01/17 06:00
MHDA- 2015/09/22 06:00
CRDT- 2015/01/17 06:00
PHST- 2014/08/07 00:00 [received]
PHST- 2014/12/24 00:00 [revised]
PHST- 2015/01/06 00:00 [accepted]
PHST- 2015/01/17 06:00 [entrez]
PHST- 2015/01/17 06:00 [pubmed]
PHST- 2015/09/22 06:00 [medline]
AID - S0166-4328(15)00014-5 [pii]
AID - 10.1016/j.bbr.2015.01.010 [doi]
PST - ppublish
SO  - Behav Brain Res. 2015 Apr 1;282:165-75. doi: 10.1016/j.bbr.2015.01.010. Epub 2015 
      Jan 13.