title: A single administration of the hallucinogen, 4-acetoxy-dimethyltryptamine, prevents the shift to a drug-dependent state and the expression of withdrawal aversions in rodents.
abstract: Despite several studies suggesting the therapeutic use of 5-hydroxytryptamine receptors type 2A (5-HT2A) agonists in the treatment of substance use disorders, the neurobiological basis accounting for such effects are still unknown. It has been observed that chronic exposure to drugs of abuse produces molecular and cellular adaptations in ventral tegmental area (VTA) neurons, mediated by brain-derived neurotrophic factor (BDNF). These BDNF-induced adaptations in the VTA are associated with the establishment of aversive withdrawal motivation that leads to a drug-dependent state. Growing evidence suggests that 5-HT2Areceptor signaling can regulate the expression of BDNF in the brain. In this study, we observed that a single systemic or intra-VTA administration of a 5-HT2Aagonist in rats and mice blocks both the aversive conditioned response to drug withdrawal and the mechanism responsible for switching from a drug-naive to a drug-dependent motivational system. Our results suggest that 5-HT2Aagonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal.
authors.affiliation: Institute of Medical Science, University of Toronto, 1130-160 College St, Toronto, ON, M5S 3E1, Canada.|The Nierika Intercultural Medicine Institute, Ocuilan, Estado de México, México.|Postgrado en Ciencias Cognitivas, Universidad Autonoma del Estado de Morelos, Cuernavaca, Morelos, México.
authors.forename: Hector
authors.identifier: 0000-0002-9907-7192
authors.initials: H
authors.lastname: Vargas-Perez
authors.affiliation: Institute of Medical Science, University of Toronto, 1130-160 College St, Toronto, ON, M5S 3E1, Canada.
authors.forename: Taryn E
authors.identifier: 0000-0003-4282-6049
authors.initials: TE
authors.lastname: Grieder
authors.affiliation: Institute of Medical Science, University of Toronto, 1130-160 College St, Toronto, ON, M5S 3E1, Canada.
authors.forename: Ryan
authors.initials: R
authors.lastname: Ting-A-Kee
authors.affiliation: Institute of Medical Science, University of Toronto, 1130-160 College St, Toronto, ON, M5S 3E1, Canada.
authors.forename: Geith
authors.initials: G
authors.lastname: Maal-Bared
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
authors.forename: Michal
authors.initials: M
authors.lastname: Chwalek
authors.affiliation: Institute of Medical Science, University of Toronto, 1130-160 College St, Toronto, ON, M5S 3E1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
authors.forename: Derek
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006213:Hallucinogens / Q000008:administration & dosage / Q000627:therapeutic use*; D006556:Heroin Dependence / Q000188:drug therapy* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004130:N,N-Dimethyltryptamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000517:prevention & control; D014363:Tryptamines / Q000008:administration & dosage / Q000627:therapeutic use*; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; D058830:Serotonin 5-HT2 Receptor Antagonists; D014363:Tryptamines; C000627026:4-acetoxy-dimethyltryptamine; D004130:N,N-Dimethyltryptamine
keywords: 
  VTA
  ; addiction; hallucinogen; neural plasticity