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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
Author(s) -
VargasPerez Hector,
Grieder Taryn E.,
TingAKee Ryan,
MaalBared Geith,
Chwalek Michal,
Kooy Derek
Publication year - 2017
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13572
Subject(s) - ventral tegmental area , agonist , drug , neuroscience , hallucinogen , self administration , neurotrophic factors , pharmacology , drug withdrawal , psychology , brain derived neurotrophic factor , receptor , medicine , dopamine , dopaminergic
Despite several studies suggesting the therapeutic use of 5‐hydroxytryptamine receptors type 2A (5‐ HT 2A ) 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‐ HT 2A receptor 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‐ HT 2A agonist 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‐ HT 2A agonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal.