| First Author | Godino A | Year | 2023 |
| Journal | Neuron | PubMed ID | 36889314 |
| Mgi Jnum | J:334720 | Mgi Id | MGI:7463889 |
| Doi | 10.1016/j.neuron.2023.02.013 | Citation | Godino A, et al. (2023) Transcriptional control of nucleus accumbens neuronal excitability by retinoid X receptor alpha tunes sensitivity to drug rewards. Neuron |
| abstractText | The complex nature of the transcriptional networks underlying addictive behaviors suggests intricate cooperation between diverse gene regulation mechanisms that go beyond canonical-activity-dependent pathways. Here, we implicate in this process a nuclear receptor transcription factor, retinoid X receptor alpha (RXRalpha), which we initially identified bioinformatically as associated with addiction-like behaviors. In the nucleus accumbens (NAc) of male and female mice, we show that although its own expression remains unaltered after cocaine exposure, RXRalpha controls plasticity- and addiction-relevant transcriptional programs in both dopamine receptor D1- and D2-expressing medium spiny neurons, which in turn modulate intrinsic excitability and synaptic activity of these NAc cell types. Behaviorally, bidirectional viral and pharmacological manipulation of RXRalpha regulates drug reward sensitivity in both non-operant and operant paradigms. Together, this study demonstrates a key role for NAc RXRalpha in promoting drug addiction and paves the way for future studies of rexinoid signaling in psychiatric disease states. |
