期刊
SCIENCE SIGNALING
卷 11, 期 512, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aam5402
关键词
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资金
- National Natural Science Foundation of China [31430033, 91632307, 31771176, 31571036, 31421091, 31400912]
- Ministry of Science and Technology [2015CB553501, 2014CB942801]
Extinction learning of cocaine-associated contextual cues can help prevent cocaine addicts from relapsing. Pharmacological manipulation of beta-adrenergic receptor (beta-AR) during extinction learning is being developed as a potential strategy to treat drug addiction. We demonstrated that the extinction learning of cocaine-associated memory was mediated by beta-arrestin2-biased but not heterotrimeric guanine nucleotide-binding protein (G protein)-dependent beta-adrenergic signaling. We found that administration of the nonbiased beta-AR antagonist propranolol, but not the G protein-biased beta-AR antagonist carvedilol, blocked extinction learning of cocaine-conditioned place preference and the associated ERK activation in the infralimbic prefrontal cortex. Overexpression of beta-arrestin2 in the infralimbic prefrontal cortex promoted extinction learning, which was blocked by propranolol. Knockout of beta-arrestin2 in the infralimbic prefrontal cortex, specifically in excitatory neurons, impaired extinction learning of cocaine-conditioned place preference, which was not rescued by carvedilol. beta-Arrestin2 signaling in infralimbic excitatory neurons was also required for the extinction learning in the cocaine self-administration model. Our results suggest that beta-arrestin-biased beta-adrenergic signaling in the infralimbic prefrontal cortex regulates extinction learning of cocaine-associated memories and could be therapeutically targeted to treat addiction.
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