Cocaine self-administration markedly increases dopamine D2 receptor negative cooperativity for dopamine binding: A receptor dimer-based analysis.

The proportion of dopamine D(2)(High) receptors has been reported to increase after cocaine self-administration without a significant change in the total number of D(2) receptors. In the present article, the data of competition by dopamine of [(3)H]domperidone binding to striatal samples from naïve and cocaine-addicted animals (Briand et al., [2008] Eur Neuropsychopharmacol 18:551-556) are analyzed assuming that D(2) receptors are constitutive dimers. The results show another way of interpreting those previous results and lead to the finding that cocaine affects agonist affinity and may strongly affect the receptor-receptor cooperation between dimers, a result that can contribute to dopamine supersensitivity.