Case Study: Presynaptic Dopaminergic Lithium

Presynaptic:
On the presynaptic dopaminergic neuron, lithium in acute administrations, inhibits the release of DA by binding onto the dopamine-specific (D1-D5) autoreceptors (Prasad, 2010). These autoreceptors serve as a mechanistic negative feedback loop that controls the release of DA and regulates its levels in the synaptic cleft. Lithium acts as an agonist on these autoreceptors and therefore inhibits the turnover of DA resulting in either increased reuptake or inhibited release from the presynaptic neuron.

However this theory had been challenged by a study conducted by Ferrie et al (2008) who investigated the effect of lithium treatment on D2/3 autoreceptor regulation in the nucleus accumbens of the rat. In one of the tests, in vitro electrophysiological analysis showed that lithium treatment did not result in a reduction in the basal stimulation of DA neurons, and, activation of the somatodentritic D2/3 autoreceptor was not observed. This suggests that that the decrease in DA levels was not due to an increase in the somatodentritic autoreceptor activity and questions the possibility of another mechanism dictating DA levels.
From this, it can be suggested that autoreceptor-mediated regulation of DA may only be attributed to acute lithium treatment and this interaction may be lost after chronic treatment. However, this lack of understanding prompts for further research in lithium’s involvement on the dopaminergic presynaptic