Overexpression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels into the Ventral Tegmental Area Increases the Rewarding Effects of Ethanol in UChB Drinking Rats
Article first published online: 24 JAN 2014
Copyright © 2014 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 38, Issue 4, pages 911–920, April 2014
How to Cite
Rivera-Meza, M., Quintanilla, M. E., Bustamante, D., Delgado, R., Buscaglia, M. and Herrera-Marschitz, M. (2014), Overexpression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels into the Ventral Tegmental Area Increases the Rewarding Effects of Ethanol in UChB Drinking Rats. Alcoholism: Clinical and Experimental Research, 38: 911–920. doi: 10.1111/acer.12344
- Issue published online: 9 APR 2014
- Article first published online: 24 JAN 2014
- Manuscript Accepted: 27 NOV 2013
- Manuscript Received: 10 AUG 2013
- FONDECYT. Grant Numbers: #3110107, #1120079, #1130012
- BNI Millenium Institute. Grant Number: #P09-015-F
- HCN Channels;
- UChB Rats;
- VTA ;
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.
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).
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).
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.