TY  - JOUR
PY  - 2019//
TI  - A mechanism linking two known vulnerability factors for alcohol abuse: heightened alcohol stimulation and low striatal dopamine D2 receptors
JO  - Cell reports
A1  - Bocarsly, Miriam E.
A1  - da Silva E Silva, Daniel
A1  - Kolb, Vanessa
A1  - Luderman, Kathryn D.
A1  - Shashikiran, Sannidhi
A1  - Rubinstein, Marcelo
A1  - Sibley, David R.
A1  - Dobbs, Lauren K.
A1  - Alvarez, Veronica A.
SP  - 1147
EP  - 1163
VL  - 29
IS  - 5
N2  - Alcohol produces both stimulant and sedative effects in humans and rodents. In humans, alcohol abuse disorder is associated with a higher stimulant and lower sedative responses to alcohol. Here, we show that this association is conserved in mice and demonstrate a causal link with another liability factor: low expression of striatal dopamine D2 receptors (D2Rs). Using transgenic mouse lines, we find that the selective loss of D2Rs on striatal medium spiny neurons enhances sensitivity to ethanol stimulation and generates resilience to ethanol sedation. These mice also display higher preference and escalation of ethanol drinking, which continues despite adverse outcomes. We find that striatal D1R activation is required for ethanol stimulation and that this signaling is enhanced in mice with low striatal D2Rs. These data demonstrate a link between two vulnerability factors for alcohol abuse and offer evidence for a mechanism in which low striatal D2Rs trigger D1R hypersensitivity, ultimately leading to compulsive-like drinking.<br><br>Published by Elsevier Inc.<p />  <p>Language: en</p>
LA  - en
SN  - 2211-1247
UR  - http://dx.doi.org/10.1016/j.celrep.2019.09.059
ID  - ref1
ER  -