Intracellular 5-HT 2C-receptor dephosphorylation: a new target for treating drug addiction.
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.
Müller
Christian P
CP
Institute of Physiological Psychology I and Center for Biological and Medical Research, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany.
Carey
Robert J
RJ
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D015696:Gene Products, tat / Q000627:therapeutic use*; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000627:therapeutic use*; D010766:Phosphorylation; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D019966:Substance-Related Disorders / Q000188:drug therapy*
D015696:Gene Products, tat; D010446:Peptide Fragments; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D051059:PTEN Phosphohydrolase; D004298:Dopamine