Cocaine inhibits 5-HT3 receptor function in neurons from transgenic mice overexpressing the receptor

Studies have shown that cocaine alters the function of recombinant 5-HT(3) receptors and that behavioral responses to cocaine are affected by 5-HT(3) receptor ligands. However, the actions of cocaine on brain 5-HT(3) receptors have not been characterized because these receptors are not abundantly expressed in most neuronal populations. We examined the effect of cocaine on 5-HT(3) receptor function in cultured hippocampal neurons from transgenic mice overexpressing the receptor. Cocaine competitively inhibited 5-HT(3) receptors with an IC(50) of approximately 4 microM, indicating that brain 5-HT(3) receptors are important targets for the actions of this commonly abused substance.