PMID- 28092019
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20210223
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 31
IP  - 4
DP  - 2017 May
TI  - URB597 and the Cannabinoid WIN55,212-2 Reduce Behavioral and Neurochemical 
      Deficits Induced by MPTP in Mice: Possible Role of Redox Modulation and NMDA 
      Receptors.
PG  - 532-544
LID - 10.1007/s12640-016-9698-1 [doi]
AB  - Several physiological events in the brain are regulated by the endocannabinoid 
      system (ECS). While synthetic cannabinoid receptor (CBr) agonists such as 
      WIN55,212-2 act directly on CBr, agents like URB597, a fatty acid amide hydrolase 
      (FAAH) inhibitor, induce a more "physiological" activation of CBr by increasing 
      the endogenous levels of the endocannabinoid anandamide (AEA). Herein, we 
      compared the pre- and post-treatment efficacy of URB597 and WIN55,212-2 on 
      different endpoints evaluated in the toxic model produced by the mitochondrial 
      toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. MPTP 
      (40 mg/kg, s.c., single injection) decreased locomotor activity, depleted the 
      striatal and nigral levels of dopamine (DA), augmented the levels of lipid 
      peroxidation and protein carbonylation in both regions, decreased the striatal 
      protein levels of tyrosine hydroxylase, and increased the striatal protein 
      content of the subunit 1 (NR1) of the N-methyl-D-aspartate receptor (NMDAr). Both 
      URB597 (0.3 mg/kg, i.p., once a day) and WIN55,212-2 (10 mug/kg, i.p., twice a 
      day), administered for five consecutive days, either before or after the MPTP 
      injection, prevented the alterations elicited by MPTP and downregulated NMDAr. 
      Our results support a modulatory role of the ECS on the toxic profile exerted by 
      MPTP in mice via the stimulation of antioxidant activity and the induction of 
      NMDAr downregulation and hypofunction, and favor the stimulation of CBr as an 
      effective experimental therapeutic strategy.
FAU - Escamilla-Ramirez, Angel
AU  - Escamilla-Ramirez A
AD  - Departamento de Neuroinmunologia, Instituto Nacional de Neurologia y 
      Neurocirugia, 14269, Mexico D.F, Mexico.
FAU - Garcia, Esperanza
AU  - Garcia E
AD  - Departamento de Neuroinmunologia, Instituto Nacional de Neurologia y 
      Neurocirugia, 14269, Mexico D.F, Mexico. egarciainnn@gmail.com.
FAU - Palencia-Hernandez, Guadalupe
AU  - Palencia-Hernandez G
AD  - Departamento de Neuroinmunologia, Instituto Nacional de Neurologia y 
      Neurocirugia, 14269, Mexico D.F, Mexico.
FAU - Colin-Gonzalez, Ana Laura
AU  - Colin-Gonzalez AL
AD  - Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurologia y 
      Neurocirugia, Insurgentes Sur 3877, 14269, Mexico City, Mexico.
FAU - Galvan-Arzate, Sonia
AU  - Galvan-Arzate S
AD  - Departamento de Neuroquimica, Instituto Nacional de Neurologia y Neurocirugia, 
      14269, Mexico D.F, Mexico.
FAU - Tunez, Isaac
AU  - Tunez I
AD  - Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina y 
      Enfermeria, Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), 
      Universidad de Cordoba, Cordoba, Spain.
FAU - Sotelo, Julio
AU  - Sotelo J
AD  - Departamento de Neuroinmunologia, Instituto Nacional de Neurologia y 
      Neurocirugia, 14269, Mexico D.F, Mexico.
FAU - Santamaria, Abel
AU  - Santamaria A
AD  - Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurologia y 
      Neurocirugia, Insurgentes Sur 3877, 14269, Mexico City, Mexico. absada@yahoo.com.
LA  - eng
PT  - Journal Article
DEP - 20170114
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Benzamides)
RN  - 0 (Benzoxazines)
RN  - 0 (Carbamates)
RN  - 0 (Morpholines)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (Naphthalenes)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester)
RN  - 5H31GI9502 
      ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Benzamides/*pharmacology
MH  - Benzoxazines/*pharmacology
MH  - Carbamates/*pharmacology
MH  - Corpus Striatum/metabolism
MH  - Dopamine/*metabolism
MH  - Down-Regulation/drug effects
MH  - Lipid Peroxidation/drug effects
MH  - Locomotion/*drug effects
MH  - MPTP Poisoning/*metabolism/prevention & control
MH  - Male
MH  - Mice
MH  - Morpholines/*pharmacology
MH  - Naphthalenes/*pharmacology
MH  - Oxidation-Reduction/drug effects
MH  - Protein Carbonylation/drug effects
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Substantia Nigra/metabolism
MH  - Tyrosine 3-Monooxygenase/metabolism
OTO - NOTNLM
OT  - Cannabinoid receptor agonists
OT  - Endocannabinoid system
OT  - MPTP toxic model
OT  - NMDAr hypofunction
OT  - Neurochemical deficits
OT  - Oxidative stress
EDAT- 2017/01/17 06:00
MHDA- 2017/10/03 06:00
CRDT- 2017/01/17 06:00
PHST- 2016/10/17 00:00 [received]
PHST- 2016/12/28 00:00 [accepted]
PHST- 2016/12/20 00:00 [revised]
PHST- 2017/01/17 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/01/17 06:00 [entrez]
AID - 10.1007/s12640-016-9698-1 [pii]
AID - 10.1007/s12640-016-9698-1 [doi]
PST - ppublish
SO  - Neurotox Res. 2017 May;31(4):532-544. doi: 10.1007/s12640-016-9698-1. Epub 2017 
      Jan 14.