PMID- 26683974
OWN - NLM
STAT- MEDLINE
DCOM- 20161005
LR  - 20181113
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Print)
IS  - 0145-6008 (Linking)
VI  - 40
IP  - 1
DP  - 2016 Jan
TI  - Chronic Intracerebroventricular Infusion of Monocyte Chemoattractant Protein-1 
      Leads to a Persistent Increase in Sweetened Ethanol Consumption During Operant 
      Self-Administration But Does Not Influence Sucrose Consumption in Long-Evans 
      Rats.
PG  - 187-95
LID - 10.1111/acer.12928 [doi]
AB  - BACKGROUND: Among the evidence implicating neuroimmune signaling in alcohol use 
      disorders are increased levels of the chemokine monocyte chemoattractant 
      protein-1 (MCP-1) in the brains of human alcoholics and animal models of alcohol 
      abuse. However, it is not known whether neuroimmune signaling can directly 
      increase ethanol (EtOH) consumption, and whether MCP-1 is involved in that 
      mechanism. We designed experiments to determine whether MCP-1 signaling itself is 
      sufficient to accelerate or increase EtOH consumption. Our hypothesis was that 
      increasing MCP-1 signaling by directly infusing it into the brain would increase 
      operant EtOH self-administration. METHODS: We implanted osmotic minipumps to 
      chronically infuse either one of several doses of MCP-1 or vehicle into the 
      cerebral ventricles (intracerebroventricular) of Long-Evans rats and then tested 
      them in the operant self-administration of a sweetened EtOH solution for 8 weeks. 
      RESULTS: There was a significant interaction between dose of MCP-1 and sweetened 
      EtOH consumed across the first 4 weeks (while pumps were flowing) and across the 
      8-week experiment. Animals receiving the highest dose of MCP-1 (2 mug/d) were the 
      highest consumers of EtOH during weeks 3 through 8. MCP-1 did not influence the 
      acquisition of self-administration (measured across the first 5 days), the 
      motivation to consume EtOH (time to lever press or progressive ratio), 
      withdrawal-induced anxiety, or the consumption of sucrose alone. CONCLUSIONS: We 
      provide novel evidence that neuroimmune signaling can directly increase chronic 
      operant EtOH self-administration, and that this increase persists beyond the 
      administration of the cytokine. These data suggest that EtOH-induced increases in 
      MCP-1, or increases in MCP-1 due to various other neuroimmune mechanisms, may 
      further promote EtOH consumption. Continued research into this mechanism, 
      particularly using models of alcohol dependence, will help determine whether 
      targeting MCP-1 signaling has therapeutic potential in the treatment of alcohol 
      use disorders.
CI  - Copyright (c) 2015 by the Research Society on Alcoholism.
FAU - Valenta, John P
AU  - Valenta JP
AD  - Division of Pharmacology/Toxicology, College of Pharmacy, The University of Texas 
      at Austin, Austin, Texas.
FAU - Gonzales, Rueben A
AU  - Gonzales RA
AD  - Division of Pharmacology/Toxicology, College of Pharmacy, The University of Texas 
      at Austin, Austin, Texas.
LA  - eng
GR  - F31 AA022284/AA/NIAAA NIH HHS/United States
GR  - R37 AA011852/AA/NIAAA NIH HHS/United States
GR  - R37 AA11852/AA/NIAAA NIH HHS/United States
PT  - Journal Article
DEP - 20151219
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Sweetening Agents)
RN  - 3K9958V90M (Ethanol)
RN  - 57-50-1 (Sucrose)
SB  - IM
MH  - Alcoholism/immunology
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Central Nervous System Depressants/*administration & dosage
MH  - Chemokine CCL2/*pharmacology
MH  - Conditioning, Operant/*drug effects
MH  - Disease Models, Animal
MH  - Ethanol/*administration & dosage
MH  - Infusions, Intraventricular
MH  - Male
MH  - Motivation
MH  - Rats
MH  - Rats, Long-Evans
MH  - Self Administration
MH  - Sucrose/*administration & dosage
MH  - Sweetening Agents/*administration & dosage
PMC - PMC4701601
MID - NIHMS731937
OTO - NOTNLM
OT  - Dopamine Neurons
OT  - Dose-Response
OT  - NF-kappaB
OT  - Neuroinflammation
OT  - Neuromodulation
EDAT- 2015/12/20 06:00
MHDA- 2016/10/07 06:00
PMCR- 2017/01/01
CRDT- 2015/12/20 06:00
PHST- 2015/06/17 00:00 [received]
PHST- 2015/10/12 00:00 [accepted]
PHST- 2015/12/20 06:00 [entrez]
PHST- 2015/12/20 06:00 [pubmed]
PHST- 2016/10/07 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.1111/acer.12928 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2016 Jan;40(1):187-95. doi: 10.1111/acer.12928. Epub 2015 
      Dec 19.