Increased serotonin prevents compulsion in addiction

Abstract

Drug addiction is a disease characterized by compulsive drug seeking and consumption despite negative consequences (1). About 20% of cocaine users lose self-control and are eventually diagnosed as addicted. Cocaine blocks dopamine, noradrenalin, and serotonin uptake through inhibition of the transporters of these neurotransmitters. The rewarding effect of cocaine is mainly induced by blocking the dopamine transporter (DAT), which increases extracellular dopamine concentrations. Intriguingly, mice that lack DAT still experience rewarding effects from cocaine, and this is abolished when both DAT and serotonin transporter (SERT) are deleted in mice (2, 3). On page 1252 of this issue, Li et al. (4) show that increased extracellular serotonin antagonizes transition to compulsive cocaine intake by inducing a presynaptic depression in which serotonin inhibits excitatory synaptic transmission to the dorsal striatum (DS) through the serotonin receptor, 5-hydroxytryptamine receptor 1B (5-HTR1B), which is expressed on the presynapse of cortical inputs.