| First Author | Gong S | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 21 | Pages | 3421-3435.e5 |
| PubMed ID | 34506723 | Mgi Jnum | J:315143 |
| Mgi Id | MGI:6830547 | Doi | 10.1016/j.neuron.2021.08.012 |
| Citation | Gong S, et al. (2021) Cocaine shifts dopamine D2 receptor sensitivity to gate conditioned behaviors. Neuron 109(21):3421-3435.e5 |
| abstractText | Cocaine addiction is a chronic, relapsing disorder characterized by maladaptation in the brain mesolimbic and nigrostriatal dopamine system. Although changes in the properties of D2-receptor-expressing medium spiny neurons (D2-MSNs) and connected striatal circuits following cocaine treatment are known, the contributions of altered D2-receptor (D2R) function in mediating the rewarding properties of cocaine remain unclear. Here, we describe how a 7-day exposure to cocaine alters dopamine signaling by selectively reducing the sensitivity, but not the expression, of nucleus accumbens D2-MSN D2Rs via an alteration in the relative expression and coupling of G protein subunits. This cocaine-induced reduction of D2R sensitivity facilitated the development of the rewarding effects of cocaine as blocking the reduction in G protein expression was sufficient to prevent cocaine-induced behavioral adaptations. These findings identify an initial maladaptive change in sensitivity by which mesolimbic dopamine signals are encoded by D2Rs following cocaine exposure. |
