Artículos de revistas
Overexpression of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels into the Ventral Tegmental Area Increases the Rewarding Effects of Ethanol in UChB Drinking Rats
Fecha
2014Registro en:
Alcohol Clin Exp Res, Vol 38, No 4, 2014: pp 911–920
DOI: 10.1111/acer.12344
Autor
Rivera Meza, Mario
Quintanilla González, María Elena
Bustamante Cádiz, Diego
Delgado Arriagada, Ricardo
Buscaglia Fernández, Marianne
Herrera-Marschitz Muller, Mario
Institución
Resumen
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.