Intracellular 5-HT 2C-receptor dephosphorylation: a new target for treating drug addiction

Abstract

The 5-hydroxytryptamine (5-HT)(2C) receptor has received considerable attention as a target for treating drug addiction. 5-HT(2C)-receptor agonism, however, also induces side-effects. In this article, we review recent findings regarding the involvement of 5-HT(2C) receptors in behaviours related to drug addiction in animals. It was recently shown that 5-HT(2C)-receptor agonist effects can be induced intracellularly using the protein peptide Tat-3L4F, which prevents 5-HT(2C)-receptor dephosphorylation induced by phosphatase and tensin homologue deleted on chromosome 10. The most promising finding is that Tat-3L4F can selectively reduce the potency of addictive drugs by reducing mesolimbic dopamine transmission without eliciting the side-effects of 5-HT(2C)-receptor agonist treatment, thus highlighting its potential use as a strategy to treat drug addiction in humans.