Scientific article
OA Policy
English

Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction

Published inNeuron, vol. 88, p. 1054-1066
Publication date2015-12
Abstract

The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc). When the mice had to endure a mild electric foot shock to obtain a stimulation, some stopped while others persevered. The resistance to punishment was associated with enhanced neural activity in the orbitofrontal cortex (OFC) while chemogenetic inhibition of the OFC reduced compulsivity. Together, these results show that stimulating VTA DA neurons induces behavioral and cellular hallmarks of addiction, indicating sufficiency for the induction and progression of the disease.

Keywords
  • Animals
  • Channelrhodopsins
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Cocaine / administration & dosage
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / pathology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins / genetics
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / physiology
  • Food Deprivation
  • GABA Antagonists / pharmacology
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / metabolism
  • Limbic System / drug effects
  • Limbic System / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism
  • Self Administration
  • Sucrose / administration & dosage
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Time Factors
Citation (ISO format)
PASCOLI, Vincent Jean et al. Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction. In: Neuron, 2015, vol. 88, p. 1054–1066. doi: 10.1016/j.neuron.2015.10.017
Main files (2)
Article (Published version)
accessLevelRestricted
Article (Accepted version)
accessLevelPublic
Secondary files (2)
Identifiers
Journal ISSN0896-6273
725views
101downloads

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First validation03/11/2015 13:24:00
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