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Cocaine receptor identified as BASP1
Author(s) -
Harraz Maged M.,
Malla Adarsha P.,
Semenza Evan R.,
Shishikura Maria,
Kang In Guk,
Snowman Adele M.,
Cortés Pedro,
Song Young Jun,
Hwang Yun,
Snyder Solomon H.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.08706
Subject(s) - nucleus accumbens , monoamine neurotransmitter , receptor , striatum , reuptake , cocaine abuse , neurochemical , pharmacology , neurotransmission , chemistry , dopamine , gambling disorder , neuroscience , biology , serotonin , biochemistry , addiction , medicine , psychiatry
Cocaine is a behavioral stimulant with substantial abuse potential related to its positively rewarding actions. Definitive molecular mechanisms of action have not been established, though cocaine is known to inhibit the reuptake inactivation of monoamine neurotransmission at high nanomolar to low micromolar concentrations. There is evidence for significantly more potent neurochemical and behavioral actions of cocaine that could not be attributed to the inhibition of monoamine transporters. Thus, evidence for a specific, high affinity cocaine receptor that mediates its behavioral actions has been lacking. In the present study we report high affinity binding of cocaine to the membrane‐associated protein BASP1, which appears to be a pharmacologically relevant cocaine receptor. Utilizing affinity pull‐down, mass spectrometry and ligand binding assays, we establish that BASP1 is a high‐affinity cocaine binding protein (Kd 7 nM). Our data show that knocking down BASP1 in the nucleus accumbens or striatum (pre‐ and post‐synaptic) inhibits behavioral actions of cocaine and reduces [3H]cocaine binding to striatal synaptosomes respectively. Taken together, our data suggest that BASP1 is a high‐affinity receptor for cocaine. Support or Funding Information Funding this work was supported by U.S. Public Health Service Grants DA00266 and DA044123 to SHS and a NARSAD Young Investigator Grant (grant # 25360) from the Brain & Behavior Foundation to MMH.