Depression: more than just serotonin

Serotonin and dopamine neurotransmitter systems in the brain are generally thought to function separately. In the presence of antidepressants that inhibit the reuptake of serotonin, however, their signals may become crossed. New research reveals that, in the presence of selective serotonin reuptake inhibitors (SSRIs), dopamine transporters may compensate to remove serotonin from the synapse.1

Figure. Photo by: Photos.com

The corpus striatum is known to affect motor coordination, motivation and reward-based learning. This area of the brain is densely packed with dopamine innervation, and it also has a moderate amount of serotonin innervation. The proximity of dopaminergic and serotoninergic neurons naturally facilitates interactions between them.2

Under normal circumstances, serotonin transporters remove serotonin from the synapse; SSRIs block these transporters and thus increase the concentration of serotonin. However, dopamine transporters are known to have a low affinity for serotonin and may therefore act as a substitute for serotonin transporters.

In a recent study, Zhou and colleagues1 demonstrated in mice that, in the presence of the SSRI fluoxetine or an excess of extracellular serotonin, dopamine nerve terminals will take up serotonin from the synapse. These neurons, which normally release only dopamine, will then release both dopamine and serotonin when they next fire. The authors suggest that this “hijacking” of dopamine transporters by serotonin may explain why it takes a few days for the effects of SSRI therapy to appear.

Serotonin is thought to play a crucial role in the pathophysiology of depression. The clinical effect of dopamine transporters in SSRI therapy is unclear, because the results described in the study by Zhou and associates do not touch upon whether dopamine and serotonin signalling interactions affect behaviour. However, they do point to dopamine transporters as an intriguing target of future study, the results of which may help in the design of new antidepressants that block the ability of dopamine receptors to uptake serotonin.