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. (4th May 2017)

• Record Type: Journal Article
• Authors: Vargas‐Perez, Hector; Grieder, Taryn E.; Ting‐A‐Kee, Ryan; Maal‐Bared, Geith; Chwalek, Michal; van der Kooy, Derek
• Editors: Majewska, Ania
• Is Part Of: European journal of neuroscience. Volume 45:Number 11(2017)
• Page Start: 1410
• Page End: 1417
• Publication Date: 2017-05-04
• Subjects: addiction -- hallucinogen -- neural plasticity -- VTA; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.13572
• Languages: English
• ISSNs: 0953-816X

Abstract

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‐HT2A 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‐HT2A 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‐HT2A agonists could be used as therapeutic agents to reverse a drug dependent state, as well as inhibiting the aversive effects produced by drug withdrawal. Abstract : The transition from a drug‐naive to a drug‐dependent and withdrawn state is a consequence of switching the neuronal substrates of drug motivation from a dopamine (DA) independent motivational system (involving the brainstem Tegmental Pedunculopontine Nucleus, TPP) to a dopamine dependent pathway, which involves the Ventral Tegmental Area (VTA) and the Nucleus Accumbens (NAcc). We observed that a single (systemic or intra‐VTA) administration of the hallucinogen 4‐AcO‐DMT prevented the switch from a drug‐naive to a drug‐dependent motivational state.