PMID- 24460767
OWN - NLM
STAT- MEDLINE
DCOM- 20141208
LR  - 20140410
IS  - 1530-0277 (Electronic)
IS  - 0145-6008 (Linking)
VI  - 38
IP  - 4
DP  - 2014 Apr
TI  - Overexpression of hyperpolarization-activated cyclic nucleotide-gated channels 
      into the ventral tegmental area increases the rewarding effects of ethanol in 
      UChB drinking rats.
PG  - 911-20
LID - 10.1111/acer.12344 [doi]
AB  - BACKGROUND: A number of studies have shown that ethanol (EtOH) activates dopamine 
      neurocircuitries and is self-administered into the ventral tegmental area (VTA) 
      of the rat brain. In vitro and in silico studies have showed that 
      hyperpolarization-activated cyclic nucleotide-gated (HCN) ionic channels on VTA 
      dopamine neurons may constitute a molecular target of EtOH; however, there is no 
      in vivo evidence supporting this assumption. METHODS: Wistar-derived University 
      of Chile Drinking (UChB) rats were microinjected into the VTA with a lentiviral 
      vector coding for rat HCN-2 ionic channel or a control vector. Four days after 
      vector administration, daily voluntary EtOH intake was assessed for 30 days under 
      a free-access paradigm to 5% EtOH and water. After EtOH consumption studies, the 
      effect of HCN-2 overexpression was also assessed on EtOH-induced conditioned 
      place preference (CPP); EtOH-induced locomotion, and EtOH-induced dopamine 
      release in the nucleus accumbens (NAcc). RESULTS: Rats microinjected with the 
      HCN-2 coding vector into the VTA showed (i) a ~2-fold increase in their voluntary 
      EtOH intake compared to control animals, (ii) lentiviral-HCN-2-treated animals 
      also showed an increased CPP to EtOH (~3-fold), (iii) a significant higher 
      locomotor activity (~2-fold), and (iv) increased dopamine release in NAcc upon 
      systemic administration of EtOH (~2-fold). CONCLUSIONS: Overexpression of HCN-2 
      ionic channel in the VTA of rats results in an increase in voluntary EtOH intake, 
      EtOH-induced CPP, locomotor activity, and dopamine release in NAcc, suggesting 
      that HCN levels in the VTA are relevant for the rewarding properties of EtOH.
CI  - Copyright (c) 2014 by the Research Society on Alcoholism.
FAU - Rivera-Meza, Mario
AU  - Rivera-Meza M
AD  - Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, 
      Faculty of Medicine, University of Chile, Santiago, Chile.
FAU - Quintanilla, Maria Elena
AU  - Quintanilla ME
FAU - Bustamante, Diego
AU  - Bustamante D
FAU - Delgado, Ricardo
AU  - Delgado R
FAU - Buscaglia, Marianne
AU  - Buscaglia M
FAU - Herrera-Marschitz, Mario
AU  - Herrera-Marschitz M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140124
PL  - England
TA  - Alcohol Clin Exp Res
JT  - Alcoholism, clinical and experimental research
JID - 7707242
RN  - 0 (Hcn2 protein, rat)
RN  - 0 (Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels)
RN  - 0 (Potassium Channels)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Alcohol Drinking/*metabolism
MH  - Animals
MH  - Ethanol/*administration & dosage
MH  - Female
MH  - *Gene Expression Regulation
MH  - HEK293 Cells
MH  - Humans
MH  - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/*biosynthesis
MH  - Potassium Channels/*biosynthesis
MH  - Rats
MH  - Rats, Wistar
MH  - *Reward
MH  - Self Administration
MH  - Ventral Tegmental Area/drug effects/*metabolism
OTO - NOTNLM
OT  - Dopamine
OT  - Ethanol
OT  - HCN Channels
OT  - UChB Rats
OT  - VTA
EDAT- 2014/01/28 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/01/28 06:00
PHST- 2013/08/10 00:00 [received]
PHST- 2013/11/27 00:00 [accepted]
PHST- 2014/01/28 06:00 [entrez]
PHST- 2014/01/28 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1111/acer.12344 [doi]
PST - ppublish
SO  - Alcohol Clin Exp Res. 2014 Apr;38(4):911-20. doi: 10.1111/acer.12344. Epub 2014 
      Jan 24.