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

Abstract

Significance Cocaine is a monoamine transport inhibitor. Current models attributing pharmacologic actions of cocaine to inhibiting the activity of the amine transporters alone failed to translate to the clinic. Cocaine inhibition of the dopamine, serotonin, and norepinephrine transporters is relatively weak, suggesting that blockade of the amine transporters alone cannot account for the actions of cocaine, especially at low doses. There is evidence for significantly more potent actions of cocaine, suggesting the existence of a high-affinity receptor(s) for the drug. Identifying and characterizing such receptors will deepen our understanding of cocaine pharmacologic actions and pave the way for therapeutic development. Here we identify a high-affinity cocaine binding site associated with BASP1 that is involved in mediating the drug’s psychotropic actions.

A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice

“…Psychostimulant effects in the brain are, in a large part (but see ref. 86 ), mediated by inhibition of Dat1 on neurons 87 . Direct DAT inhibition increases extracellular dopamine availability, thus causing excess excitation that evokes hyperlocomotion.…”