PMID- 33595955
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20230910
IS  - 1473-5849 (Electronic)
IS  - 0955-8810 (Print)
IS  - 0955-8810 (Linking)
VI  - 32
IP  - 4
DP  - 2021 Jun 1
TI  - Subanesthetic ketamine with an AMPAkine attenuates motor impulsivity in rats.
PG  - 335-344
LID - 10.1097/FBP.0000000000000623 [doi]
AB  - The concept of 'impulse control' has its roots in early psychiatry and today has 
      progressed into a well-described, although poorly understood, multidimensional 
      endophenotype underlying many neuropsychiatric disorders (e.g., attention deficit 
      hyperactivity disorder, schizophrenia, substance use disorders). There is 
      mounting evidence suggesting that the cognitive and/or behavioral dimensions 
      underlying impulsivity are driven by dysfunctional glutamate (Glu) 
      neurotransmission via targeted ionotropic Glu receptor (GluR) [e.g., 
      N-methyl-D-aspartate receptor (NMDAR), 
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)] mechanisms 
      and associated synaptic alterations within key brain nodes. Ketamine, a 
      noncompetitive NMDAR antagonist and FDA-approved for treatment-resistant 
      depression, induces a 'glutamate burst' that drives resculpting of the synaptic 
      milieu, which lasts for several days to a week. Thus, we hypothesized that single 
      and repeated treatment with a subanesthetic ketamine dose would normalize motor 
      impulsivity. Next, we hypothesized that AMPAR positive allosteric modulation, 
      alone or in combination with ketamine, would attenuate impulsivity and provide 
      insight into the mechanisms underlying GluR dysfunction relevant to motor 
      impulsivity. To measure motor impulsivity, outbred male Sprague-Dawley rats were 
      trained on the one-choice serial reaction time task. Rats pretreated with single 
      or repeated (3 days) administration of ketamine (10 mg/kg; i.p.; 24-h 
      pretreatment) or with the AMPAkine HJC0122 (1 or 10 mg/kg; i.p.; 30-min 
      pretreatment) exhibited lower levels of motor impulsivity vs. control. 
      Combination of single or repeated ketamine plus HJC0122 also attenuated motor 
      impulsivity vs. control. We conclude that ligands designed to promote GluR 
      signaling represent an effective pharmacological approach to normalize 
      impulsivity and subsequently, neuropsychiatric disorders marked by aberrant 
      impulse control.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Davis-Reyes, Brionna D
AU  - Davis-Reyes BD
AD  - Center for Addiction Research and Department of Pharmacology and Toxicology, 
      University of Texas Medical Branch, Galveston, Texas, USA.
FAU - Smith, Ashley E
AU  - Smith AE
FAU - Xu, Jimin
AU  - Xu J
FAU - Cunningham, Kathryn A
AU  - Cunningham KA
FAU - Zhou, Jia
AU  - Zhou J
FAU - Anastasio, Noelle C
AU  - Anastasio NC
LA  - eng
GR  - R00 DA033374/DA/NIDA NIH HHS/United States
GR  - T32 DA007287/DA/NIDA NIH HHS/United States
GR  - U18 DA052545/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Behav Pharmacol
JT  - Behavioural pharmacology
JID - 9013016
RN  - 0 (Antidepressive Agents)
RN  - 0 (Nootropic Agents)
RN  - 0 (Pyrrolidinones)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid subtype glutamate 
      receptor, human)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 5L16LKN964 (aniracetam)
RN  - 690G0D6V8H (Ketamine)
RN  - ZH516LNZ10 (Piracetam)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Cognition/drug effects/physiology
MH  - Dose-Response Relationship, Drug
MH  - Glutamic Acid/*metabolism
MH  - *Impulsive Behavior/drug effects/physiology
MH  - Ketamine/*pharmacology
MH  - *Mental Disorders/drug therapy/metabolism/psychology
MH  - Neuronal Plasticity/drug effects
MH  - Nootropic Agents/pharmacology
MH  - Piracetam/*pharmacology
MH  - Pyrrolidinones/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glutamate/*metabolism
MH  - *Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism
MH  - Synaptic Transmission/drug effects/physiology
PMC - PMC8119302
MID - NIHMS1660906
EDAT- 2021/02/18 06:00
MHDA- 2022/01/27 06:00
PMCR- 2022/06/01
CRDT- 2021/02/17 14:09
PHST- 2021/02/18 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/02/17 14:09 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 00008877-202106000-00008 [pii]
AID - 10.1097/FBP.0000000000000623 [doi]
PST - ppublish
SO  - Behav Pharmacol. 2021 Jun 1;32(4):335-344. doi: 10.1097/FBP.0000000000000623.