Cocaine modulates allosteric D 2-σ 1 receptor-receptor interactions on dopamine and glutamate nerve terminals from rat striatum

摘要

AbstractThe effects of nanomolar cocaine concentrations, possibly not blocking the dopamine transporter activity, on striatal D2-σ1heteroreceptor complexes and their inhibitory signaling over Gi/o, have been tested in rat striatal synaptosomes and HEK293T cells. Furthermore, the possible role of σ1receptors (σ1Rs) in the cocaine-provoked amplification of D2receptor (D2R)-induced reduction of K+-evoked [3H]-DA and glutamate release from rat striatal synaptosomes, has also been investigated.The dopamine D2-likeR agonist quinpirole (10nM–1μM), concentration-dependently reduced K+-evoked [3H]-DA and glutamate release from rat striatal synaptosomes. The σ1R antagonist BD1063 (100nM), amplified the effects of quinpirole (10 and 100nM) on K+-evoked [3H]-DA, but not glutamate, release.Nanomolar cocaine concentrations significantly enhanced the quinpirole (100nM)-induced decrease of K+-evoked [3H]-DA and glutamate release from rat striatal synaptosomes. In the presence of BD1063 (10nM), cocaine failed to amplify the quinpirole (100nM)-induced effects.In cotransfected σ