Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus drive onto dopamine neurons in Sardinian alcohol-preferring rats.
Journal of Neuroscience. 2014-09-17; 34(38): 12716-12724
DOI: 10.1523/jneurosci.1844-14.2014
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1. J Neurosci. 2014 Sep 17;34(38):12716-24. doi: 10.1523/JNEUROSCI.1844-14.2014.
Enhanced endocannabinoid-mediated modulation of rostromedial tegmental nucleus
drive onto dopamine neurons in Sardinian alcohol-preferring rats.
Melis M(1), Sagheddu C(2), De Felice M(2), Casti A(2), Madeddu C(2), Spiga S(3),
Muntoni AL(4), Mackie K(5), Marsicano G(6), Colombo G(4), Castelli MP(2), Pistis
M(7).
Author information:
(1)Division of Neuroscience and Clinical Pharmacology, Department of Biomedical
Sciences, University of Cagliari, 09042 Monserrato, Italy, .
(2)Division of Neuroscience and Clinical Pharmacology, Department of Biomedical
Sciences, University of Cagliari, 09042 Monserrato, Italy.
(3)Department of Life and Environment Science, University of Cagliari, 09126
Cagliari, Italy.
(4)Neuroscience Institute, National Research Council of Italy, Section of
Cagliari, 09126 Cagliari Italy.
(5)Department of Psychological and Brain Sciences, Gill Center for Biomolecular
Sciences, Indiana University of Bloomington, Bloomington, Indiana 47405.
(6)INSERM, U862 NeuroCentre Magendie, Endocannabinoids and Neuroadaptation, 33077
Bordeaux, France, and University of Bordeaux, NeuroCentre Magendie U862, 33077
Bordeaux, France.
(7)Division of Neuroscience and Clinical Pharmacology, Department of Biomedical
Sciences, University of Cagliari, 09042 Monserrato, Italy, Neuroscience
Institute, National Research Council of Italy, Section of Cagliari, 09126
Cagliari Italy.
The progressive predominance of rewarding effects of addictive drugs over their
aversive properties likely contributes to the transition from drug use to drug
dependence. By inhibiting the activity of DA neurons in the VTA, GABA projections
from the rostromedial tegmental nucleus (RMTg) are well suited to shift the
balance between drug-induced reward and aversion. Since cannabinoids suppress
RMTg inputs to DA cells and CB1 receptors affect alcohol intake in rodents, we
hypothesized that the endocannabinoid system, by modulating this pathway, might
contribute to alcohol preference. Here we found that RMTg afferents onto VTA DA
neurons express CB1 receptors and display a 2-arachidonoylglycerol
(2-AG)-dependent form of short-term plasticity, that is, depolarization-induced
suppression of inhibition (DSI). Next, we compared rodents with innate opposite
alcohol preference, the Sardinian alcohol-preferring (sP) and
alcohol-nonpreferring (sNP) rats. We found that DA cells from alcohol-naive sP
rats displayed a decreased probability of GABA release and a larger DSI. This
difference was due to the rate of 2-AG degradation. In vivo, we found a reduced
RMTg-induced inhibition of putative DA neurons in sP rats that negatively
correlated with an increased firing. Finally, alcohol failed to enhance RMTg
spontaneous activity and to prolong RMTg-induced silencing of putative DA neurons
in sP rats. Our results indicate functional modifications of RMTg projections to
DA neurons that might impact the reward/aversion balance of alcohol attributes,
which may contribute to the innate preference observed in sP rats and to their
elevated alcohol intake.
Copyright © 2014 the authors 0270-6474/14/3412716-09$15.00/0.
DOI: 10.1523/JNEUROSCI.1844-14.2014
PMCID: PMC4166158
PMID: 25232109 [Indexed for MEDLINE]