PMID- 24236947
OWN - NLM
STAT- MEDLINE
DCOM- 20141007
LR  - 20211021
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 171
IP  - 3
DP  - 2014 Feb
TI  - GluN2C/GluN2D subunit-selective NMDA receptor potentiator CIQ reverses 
      MK-801-induced impairment in prepulse inhibition and working memory in Y-maze 
      test in mice.
PG  - 799-809
LID - 10.1111/bph.12518 [doi]
AB  - BACKGROUND AND PURPOSE: Despite ample evidence supporting the 
      N-methyl-D-aspartate receptor (NMDAR) hypofunction hypothesis of schizophrenia, 
      progress in the development of effective therapeutics based on this hypothesis 
      has been limited. Facilitation of NMDA receptor function by co-agonists (D-serine 
      or glycine) only partially alleviates the symptoms in schizophrenia; other means 
      to facilitate NMDA receptors are required. NMDA receptor sub-types differ in 
      their subunit composition, with varied GluN2 subunits (GluN2A-GluN2D) imparting 
      different physiological, biochemical and pharmacological properties. CIQ is a 
      positive allosteric modulator that is selective for GluN2C/GluN2D-containing NMDA 
      receptors (Mullasseril et al.). EXPERIMENTAL APPROACH: The effect of systemic 
      administration of CIQ was tested on impairment in prepulse inhibition (PPI), 
      hyperlocomotion and stereotypy induced by i.p. administration of MK-801 and 
      methamphetamine. The effect of CIQ was also tested on MK-801-induced impairment 
      in working memory in Y-maze spontaneous alternation test. KEY RESULTS: We found 
      that systemic administration of CIQ (20 mg.kg(-)(1), i.p.) in mice reversed MK-801 
      (0.15 mg.kg(-)(1), i.p.)-induced, but not methamphetamine (3 mg.kg(-)(1), i.p.)-induced, 
      deficit in PPI. MK-801 increased the startle amplitude to pulse alone, which was 
      not reversed by CIQ. In contrast, methamphetamine reduced the startle amplitude 
      to pulse alone, which was reversed by CIQ. CIQ also partially attenuated MK-801- 
      and methamphetamine-induced hyperlocomotion and stereotyped behaviours. 
      Additionally, CIQ reversed the MK-801-induced working memory deficit in 
      spontaneous alternation in a Y-maze. CONCLUSION AND IMPLICATIONS: Together, these 
      results suggest that facilitation of GluN2C/GluN2D-containing receptors may serve 
      as an important therapeutic strategy for treating positive and cognitive symptoms 
      in schizophrenia.
CI  - (c) 2013 The British Pharmacological Society.
FAU - Suryavanshi, P S
AU  - Suryavanshi PS
AD  - Department of Pharmacology, Creighton University, Omaha, NE, USA.
FAU - Ugale, R R
AU  - Ugale RR
FAU - Yilmazer-Hanke, D
AU  - Yilmazer-Hanke D
FAU - Stairs, D J
AU  - Stairs DJ
FAU - Dravid, S M
AU  - Dravid SM
LA  - eng
GR  - G20 RR024001/RR/NCRR NIH HHS/United States
GR  - G20RR024001/RR/NCRR NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 
      ((3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone)
RN  - 0 (Isoquinolines)
RN  - 0 (NR2C NMDA receptor)
RN  - 0 (NR2D NMDA receptor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nootropic Agents)
RN  - 0 (Protein Subunits)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Allosteric Regulation/drug effects
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Cognition Disorders/etiology/prevention & control
MH  - *Disease Models, Animal
MH  - Dizocilpine Maleate
MH  - Hyperkinesis/etiology/prevention & control
MH  - Isoquinolines/*therapeutic use
MH  - Male
MH  - Maze Learning/drug effects
MH  - Memory, Short-Term/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Motor Activity/drug effects
MH  - Nerve Tissue Proteins/agonists/chemistry/metabolism
MH  - Neural Inhibition/drug effects
MH  - Neuroprotective Agents/*therapeutic use
MH  - Nootropic Agents/*therapeutic use
MH  - Protein Subunits/agonists/chemistry/metabolism
MH  - Quinolines/*therapeutic use
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/chemistry/metabolism
MH  - Schizophrenia/*drug therapy/physiopathology
PMC - PMC3969090
OTO - NOTNLM
OT  - CIQ
OT  - GRIN2C
OT  - GRIN2D
OT  - GluN2C
OT  - GluN2D
OT  - NMDA receptor
OT  - prepulse inhibition
OT  - schizophrenia
OT  - working memory in Y-maze
EDAT- 2013/11/19 06:00
MHDA- 2014/10/08 06:00
PMCR- 2015/02/01
CRDT- 2013/11/19 06:00
PHST- 2013/07/04 00:00 [received]
PHST- 2013/11/07 00:00 [revised]
PHST- 2013/11/12 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/10/08 06:00 [medline]
PHST- 2015/02/01 00:00 [pmc-release]
AID - 10.1111/bph.12518 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2014 Feb;171(3):799-809. doi: 10.1111/bph.12518.