The abused inhalant toluene increases dopamine release in the nucleus accumbens by directly stimulating ventral tegmental area neurons

Neuropsychopharmacology. 2007 Jul;32(7):1558-69. doi: 10.1038/sj.npp.1301273. Epub 2007 Jan 10.


Recreational abuse of toluene-containing volatile inhalants by adolescents is a significant public health problem. The mechanisms underlying the abuse potential of such substances remain unclear, but could involve increased activity in mesoaccumbal dopamine (DA) afferents innervating the nucleus accumbens (ACB). Here, using in vitro electrophysiology, we show that application of behaviorally relevant concentrations of toluene directly stimulates DA neurons in the ventral tegmental area (VTA), but not surrounding midbrain regions. Toluene stimulation of VTA neurons persists when synaptic transmission is reduced. Moreover, unlike non-DA neurons, the magnitude of VTA DA neuron firing does not decline during longer exposures designed to emulate 'huffing'. Using dual-probe in vivo microdialysis, we show that perfusion of toluene directly into the VTA increases DA concentrations in the VTA (somatodendritic release) and its terminal projection site, the ACB. These results provide the first demonstration that even brief exposure to toluene increases action potential drive onto mesoaccumbal VTA DA neurons, thereby enhancing DA release in the ACB. The finding that toluene stimulates mesoaccumbal neurotransmission by activating VTA DA neurons directly (independently of transynaptic inputs) provide insights into the neural substrates that may contribute to the initiation and pathophysiology of toluene abuse.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Dopamine / metabolism*
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Inhalation Exposure / adverse effects*
  • Male
  • Microdialysis
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Organ Culture Techniques
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reward
  • Solvents / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Toluene / pharmacology*
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / metabolism


  • Solvents
  • Toluene
  • Dopamine