A portion of [3H]cocaine binding in brain is associated with serotonergic neurons

Three lines of evidence are brought forward in support of an association in the brain cortex of some, but not all, of the cocaine binding sites with serotonergic nerve terminals. The first is based upon the significant correlation observed between the inhibition of cocaine binding by various drugs and the inhibition of neuronal uptake of serotonin in the mouse cerebral cortex. The second is based upon the demonstration of cocaine binding in human blood platelets, a model system for central serotonergic neurons. The third comes from experiments in which rats were treated with p-chloroamphetamine and 5,7-dihydroxytryptamine (serotonin neurotoxins), 6-hydroxydopamine (catecholamine neurotoxin), or p-chlorophenylalanine (inhibitor of tryptophan hydroxylase). Only the serotonin neurotoxins decreased the binding of [3H]cocaine in the rat cerebral cortex, but to a lower extent than the binding of [3]imipramine, which is known to be associated with serotonergic terminals. In contrast to the cocaine binding in the mouse cerebral cortex, the binding in the rat cerebral cortex included a considerable portion of low-affinity binding that was relatively unaffected by lesions of serotonergic neurons.