SLC18A2 is essential for enabling the release of neurotransmitters from the axon terminals of monoamine neurons into the synaptic cleft. If SLC18A2 function is inhibited or compromised, monoamine neurotransmitters such as dopamine cannot be released into the synapse via typical release mechanisms (i.e., exocytosis resulting from action potentials).
Cocaine users display a marked reduction in SLC18A2 immunoreactivity. Those with cocaine-induced mood disorders displayed a significant loss of SLC18A2 immunoreactivity; this might reflect damage to dopamine axon terminals in the striatum. These neuronal changes could play a role in causing disordered mood and motivational processes in more severely addicted users.