A high-affinity cocaine binding site associated with the brain acid soluble protein 1

Proc Natl Acad Sci U S A. 2022 Apr 19;119(16):e2200545119. doi: 10.1073/pnas.2200545119. Epub 2022 Apr 11.


Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine’s behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

Keywords: BASP1; behavior; cocaine; drug abuse; receptor.

MeSH terms

  • Animals
  • Binding Sites
  • Calmodulin-Binding Proteins* / genetics
  • Calmodulin-Binding Proteins* / metabolism
  • Carrier Proteins* / genetics
  • Carrier Proteins* / metabolism
  • Cocaine* / metabolism
  • Cocaine* / pharmacology
  • Corpus Striatum / metabolism
  • Cytoskeletal Proteins* / genetics
  • Cytoskeletal Proteins* / metabolism
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Gene Knock-In Techniques
  • Humans
  • Mice
  • Nerve Tissue Proteins* / genetics
  • Nerve Tissue Proteins* / metabolism
  • Rats
  • Receptors, Drug* / genetics
  • Receptors, Drug* / metabolism


  • Basp1 protein, mouse
  • Calmodulin-Binding Proteins
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Drug
  • cocaine receptor
  • Cocaine
  • Dopamine