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

Inhalant abuse is a common, potentially lethal, form of drug abuse. Although the putative psychotropic compo- nent 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 rnin.) concentrations of toluene vapor (1 1,500 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%,t72%; 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 concen- trations (4-79 pg/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. The widespread abuse of inhalants (i.e., spray paints, glues, and lacquers) is a significant and potentially lethal problem among youth. An epidemiological study showed that in 1995, 23% of the adolescents in the United States were ex- perimenting with inhalants (Mathias 1996). Notably, up- wards of 38% of users may die during their first inhalant experience (Flanagan & Ives 1994). Although inhalant use may also lead to the abuse of other substances, a significant percentage of users prefer and continue to abuse inhalants to the point of irreversible neurotoxic consequences (Delva et ul. 1997). Although the overall incidence of inhalant abuse is extensive there is little experimental data implicat- ing the abuse liability of solvents such as toluene with a specific CNS site or mechanism of action. The acute consumption of inhalants produces a variety of psychotropic effects including an initial euphoria, intoxi- cation, slurred speech, ataxia, numbness of the extremities, amnesia, hostile behaviour, and hallucinations. As inhal- ation continues, seizures, tinnitus, diffuse somatic pain, tremor, and death can occur (Flanagan & Ives 1994). Sev- eral reports also link chronic "huffing" to permanent liver, kidney, heart and cranial nerve damage, cerebral, cerebellar, and brainstem atrophy, neuropathies, dependence, and psy- chosis (for a review see Arlien-S~rborg 1992). Many consider the organic solvent toluene the essential psychotropic com- ponent found in the more commonly abused inhalants. Even non-human primates lever press for bursts of toluene