title: Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders.
abstract: BACKGROUND
  There are currently no treatments approved by the FDA to effectively treat cocaine dependence. Research of recent years has gradually revealed the importance of 5-hydroxytryptamine (5-HT) in the reinforcing and rewarding effects of cocaine and the potential for relapse. Brain-derived neurotropic factor (BDNF) is an important modulator of the serotonergic system and 5-HT modulates BDNF expression. Their reciprocal interaction is of crucial importance for synaptic plasticity during long-term cocaine intake. Thus, agents modifying BDNF-5-HT interactions might have therapeutic potential for cocaine dependence by reversing the altered brain structure that underlies relapse after cocaine withdrawal.
  
  
  METHODS
  On the basis of the available literature, the authors propose an interaction between BDNF and the serotonergic system in the response to cocaine and during cocaine intake. Furthermore, they discuss putative therapies that are based on 5-HT and BDNF.
  
  
  CONCLUSIONS
  Recent studies are beginning to elucidate the role of 5-HT and BDNF in cocaine addiction. Additionally, animal studies modeling addiction-like drug intake will only further help to gain a better understanding of how to treat cocaine addiction. Based on the current evidence, the authors believe that BDNF, as a modulator of the serotonergic pathway, or 5-HT, as a modulator of the BDNF system, represent a valuable target to treat drug addiction, which may yield novel therapeutics in the future.
authors.affiliation: Radboud University Medical Centre , Nijmegen, Geert Grooteplein 21 (route 126), 6525 EZ , The Netherlands +31 24 3610906 ; Judith.Homberg@radboudumc.nl.
authors.forename: Sandra M W
authors.initials: SM
authors.lastname: van de Wiel
authors.forename: Michel M
authors.initials: MM
authors.lastname: Verheij
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018490:Serotonin Agents; D012701:Serotonin
keywords: 5-HT; brain-derived neurotropic factor; cocaine addiction; epigenetics; nucleus accumbens