A red nucleus-VTA glutamate pathway underlies exercise reward and the therapeutic effect of exercise on cocaine use. Sci Adv 2022 Sep 02;8(35):eabo1440
Date
09/03/2022Pubmed ID
36054363Pubmed Central ID
PMC10848951DOI
10.1126/sciadv.abo1440Scopus ID
2-s2.0-85137156932 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Physical exercise is rewarding and protective against drug abuse and addiction. However, the neural mechanisms underlying these actions remain unclear. Here, we report that long-term wheel-running produced a more robust increase in c-fos expression in the red nucleus (RN) than in other brain regions. Anatomic and functional assays demonstrated that most RN magnocellular portion (RNm) neurons are glutamatergic. Wheel-running activates a subset of RNm glutamate neurons that project to ventral tegmental area (VTA) dopamine neurons. Optogenetic stimulation of this pathway was rewarding, as assessed by intracranial self-stimulation and conditioned place preference, whereas optical inhibition blocked wheel-running behavior. Running wheel access decreased cocaine self-administration and cocaine seeking during extinction. Last, optogenetic stimulation of the RNm-to-VTA glutamate pathway inhibited responding to cocaine. Together, these findings indicate that physical exercise activates a specific RNm-to-VTA glutamatergic pathway, producing exercise reward and reducing cocaine intake.
