PMID- 37375760
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230701
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 16
IP  - 6
DP  - 2023 May 30
TI  - NMDA Receptor Glycine Binding Site Modulators for Prevention and Treatment of 
      Ketamine Use Disorder.
LID - 10.3390/ph16060812 [doi]
LID - 812
AB  - Ketamine offers a fast-acting approach to relieving treatment-resistant 
      depression, but its abuse potential is an issue of concern. As ketamine is a 
      noncompetitive N-methyl-D-aspartate receptor (NMDAR) ion channel blocker, 
      modulation of NMDAR might be an effective strategy to counteract the abuse 
      liability of ketamine and even to treat ketamine use disorder. This study 
      evaluated whether NMDAR modulators that act on glycine binding sites can decrease 
      motivation to obtain ketamine and reduce reinstatement to ketamine-seeking 
      behavior. Two NMDAR modulators, D-serine and sarcosine were examined. Male 
      Sprague-Dawley rats underwent training to acquire the ability to self-administer 
      ketamine. The motivation to self-administer ketamine or sucrose pellets was 
      examined under a progressive ratio (PR) schedule. The reinstatement of 
      ketamine-seeking and sucrose pellet-seeking behaviors were assessed after 
      extinction. The results showed that both D-serine and sarcosine significantly 
      decreased the breakpoints for ketamine and prevented reinstatement of ketamine 
      seeking. However, these modulators did not alter motivated behavior for sucrose 
      pellets, the ability of the cue and sucrose pellets to reinstate sucrose-seeking 
      behavior or spontaneous locomotor activity. These findings indicate that two 
      NMDAR modulators can specifically reduce the measures of motivation and relapse 
      for ketamine in rats, suggesting that targeting the glycine binding site of the 
      NMDAR is a promising approach for preventing and treating ketamine use disorder.
FAU - Hsiao, Yu-Chin
AU  - Hsiao YC
AD  - Center for Neuropsychiatric Research, National Health Research Institutes, 35 
      Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
FAU - Lee, Mei-Yi
AU  - Lee MY
AD  - Center for Neuropsychiatric Research, National Health Research Institutes, 35 
      Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
FAU - Chan, Ming-Huan
AU  - Chan MH
AD  - Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, 
      Wenshan District, Taipei City 11605, Taiwan.
AD  - Research Center for Mind, Brain, and Learning, National Chengchi University, 64, 
      Sec. 2, ZhiNan Road, Wenshan District, Taipei City 11605, Taiwan.
FAU - Chen, Hwei-Hsien
AU  - Chen HH
AUID- ORCID: 0000-0002-8509-6448
AD  - Center for Neuropsychiatric Research, National Health Research Institutes, 35 
      Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
AD  - Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, 
      Wenshan District, Taipei City 11605, Taiwan.
LA  - eng
GR  - NSC-108-2314-B-400-034-MY3/National Scientific and Technical Research Council/
GR  - NP-108-PP05/National Health Research Institutes/
PT  - Journal Article
DEP - 20230530
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC10305354
OTO - NOTNLM
OT  - D-serine
OT  - breakpoint
OT  - reinstatement
OT  - sarcosine
OT  - sucrose
COIS- The authors declare that they have no conflict of interest to disclose.
EDAT- 2023/06/28 06:42
MHDA- 2023/06/28 06:43
PMCR- 2023/05/30
CRDT- 2023/06/28 01:35
PHST- 2023/04/26 00:00 [received]
PHST- 2023/05/26 00:00 [revised]
PHST- 2023/05/26 00:00 [accepted]
PHST- 2023/06/28 06:43 [medline]
PHST- 2023/06/28 06:42 [pubmed]
PHST- 2023/06/28 01:35 [entrez]
PHST- 2023/05/30 00:00 [pmc-release]
AID - ph16060812 [pii]
AID - pharmaceuticals-16-00812 [pii]
AID - 10.3390/ph16060812 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2023 May 30;16(6):812. doi: 10.3390/ph16060812.