An electrophysiological analysis of rat ventral tegmental dopamine neuronal activity during acute toluene exposure.

Abstract

Inhalant abuse is a common, potentially lethal, form of drug abuse. Although the putative psychotropic component of some popularly abused inhalants appears often to be the organic solvent toluene, its effects on midbrain neurones which comprise reward pathways have not been established. Therefore, the present study was designed to assess the response of ventral tegmental dopamine neurones during toluene inhalation. Electrophysiological determinations were made using extracellular single-unit recordings in ketamine anaesthetized rats that were exposed to acute (1-15.3 min.) concentrations of toluene vapor (11,500 ppm) similar to those consumed by inhalant abusers. Toluene exposure through a tracheal breathing tube elicited two distinctly different patterns of response in dopamine neurons. One pattern consisted of an initial stimulation of neuronal firing (+221%+/-72%; <8.5 min.) followed by an attenuation of the firing rate with continued exposure (+58.7%+/-6.3%; >8.5 min.). The other pattern consisted of only an inhibition of firing regardless of the length of exposure. Furthermore, the changes in firing rates were paralleled by changes in number of action potentials contained in bursts. Blood samples taken at the time of the dopamine recordings revealed comparable toluene concentrations (4-79 microg/ml, n=24) regardless of the patterns of response. These results suggest that mesolimbic dopamine neurotransmission can be changed by an exposure paradigm comparable to that used by human abusers, and that these changes may be integral to the reinforcing effects underlying inhalant abuse.