PMID- 25421513
OWN - NLM
STAT- MEDLINE
DCOM- 20150720
LR  - 20181113
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 38
IP  - 11
DP  - 2014 Nov
TI  - Ethanol attenuation of long-term depression in the nucleus accumbens can be 
      overcome by activation of TRPV1 receptors.
PG  - 2763-9
LID - 10.1111/acer.12542 [doi]
AB  - BACKGROUND: Altered expression of synaptic plasticity within the nucleus 
      accumbens (NAc) constitutes a critical neuroadaptive response to ethanol (EtOH) 
      and other drugs of abuse. We have previously reported that N-methyl-D-aspartate 
      receptor (NMDAR)-dependent long-term depression (LTD) is markedly affected by 
      chronic intermittent ethanol exposure in vivo; however, endocannabinoid 
      (eCB)-dependent synaptic depression, despite being very well-documented in the 
      dorsal striatum, is much less well understood in the NAc. METHODS: Whole cell 
      patch clamp electrophysiology was used to investigate interactions between these 
      different plasticity-induction systems. Excitatory postsynaptic currents (EPSCs) 
      were measured in the NAc shell and NMDAR-LTD was induced by a pairing protocol 
      (500 stimuli at 1 Hz stimulation [low-frequency stimulation (LFS)] paired with 
      postsynaptic depolarization to -50 mV). AM251, a CB1 receptor antagonist, was 
      used to determine whether this form of LTD is modulated by eCBs. To determine the 
      effect of EtOH on a purely eCB-dependent response in the NAc, 
      depolarization-induced suppression of excitation (DSE) was used in the presence 
      of 40 mM EtOH. Finally, we determined whether the enhancement of eCB signaling 
      with URB597, a fatty acid amide hydrolase inhibitor, and AM404, an anandamide 
      re-uptake inhibitor would also modulate LFS LTD in the presence of NMDAR blockade 
      or EtOH. RESULTS: In the presence of AM251, the LFS pairing protocol resulted in 
      NMDAR-dependent long-term potentiation that was blocked with either EtOH or 
      DL-APV. We also found that DSE in the NAc shell was blocked by AM251 and 
      suppressed by EtOH. Enhanced eCB signaling rescued NAc-LTD expression in the 
      presence of EtOH through a distinct mechanism requiring activation of TRPV1 
      receptors. CONCLUSIONS: EtOH modulation of synaptic plasticity in the NAc is 
      dependent upon a complex interplay between NMDARs, eCBs, and TRPV1 receptors. 
      These findings demonstrate a novel form of TRPV1-dependent LTD in the NAc shell 
      that may be critical for EtOH dependence.
CI  - Copyright (c) 2014 by the Research Society on Alcoholism.
FAU - Renteria, Rafael
AU  - Renteria R
AD  - Institute for Neuroscience, The College of Pharmacy, The University of Texas at 
      Austin, Austin, Texas.
FAU - Jeanes, Zachary M
AU  - Jeanes ZM
FAU - Morrisett, Richard A
AU  - Morrisett RA
LA  - eng
GR  - R01AA15167/AA/NIAAA NIH HHS/United States
GR  - T32 AA007471/AA/NIAAA NIH HHS/United States
GR  - T32 AA07471/AA/NIAAA NIH HHS/United States
GR  - U01 AA016651/AA/NIAAA NIH HHS/United States
GR  - R01 AA015167/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Piperidines)
RN  - 0 (Pyrazoles)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 receptor)
RN  - 3I4FA44MAI (AM 251)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Ethanol/*pharmacology
MH  - Long-Term Synaptic Depression/drug effects/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nucleus Accumbens/drug effects/*metabolism
MH  - Organ Culture Techniques
MH  - Piperidines/pharmacology
MH  - Pyrazoles/pharmacology
MH  - TRPV Cation Channels/antagonists & inhibitors/*metabolism
PMC - PMC4244656
MID - NIHMS623278
OTO - NOTNLM
OT  - Depolarization-Induced Suppression of Excitation
OT  - Electrophysiology
OT  - Endocannabinoid
OT  - Plasticity
OT  - TRPV1
EDAT- 2014/11/26 06:00
MHDA- 2015/07/21 06:00
PMCR- 2015/11/01
CRDT- 2014/11/26 06:00
PHST- 2014/03/23 00:00 [received]
PHST- 2014/08/06 00:00 [accepted]
PHST- 2014/11/26 06:00 [entrez]
PHST- 2014/11/26 06:00 [pubmed]
PHST- 2015/07/21 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - 10.1111/acer.12542 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2014 Nov;38(11):2763-9. doi: 10.1111/acer.12542.