Striatal dopamine dynamics in mice following acute and repeated toluene exposure
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The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Available evidence suggests that toluene inhalation alters dopamine (DA) neurotransmission, but toluene’s mechanism of action is unknown.
The present study evaluated the effect of acute and repeated toluene inhalation (0, 2,000, or 4,000 ppm) on locomotor activity as well as striatal DA release and uptake using slice fast-scan cyclic voltammetry.
Acutely, 2,000 and 4,000 ppm toluene increased locomotor activity, while neurochemically only 4,000 ppm toluene potentiated electrically evoked DA release across the caudate-putamen and the nucleus accumbens. Repeated administration of toluene resulted in sensitization to toluene’s locomotor activity effects. Brain slices obtained from mice repeatedly exposed to toluene demonstrated no difference in stimulated DA release in the caudate-putamen as compared to control animals. Repeated exposure to 2,000 and 4,000 ppm toluene caused a concentration-dependent decrease of 25–50 % in evoked DA release in the nucleus accumbens core and shell relative to air-exposed mice.
These voltammetric neurochemical findings following repeated toluene exposure suggest that there may be a compensatory downregulation of the DA system. Acute or repeated toluene exposure had no effect on the DA uptake kinetics. Taken together, these results demonstrate that acute toluene inhalation potentiates DA release, while repeated toluene exposure attenuates DA release in the nucleus accumbens only.
KeywordsMice Toluene Caudate-putamen Nucleus accumbens Locomotor activity Fast-scan cyclic voltammetry
This work was supported by WSU Start Up Funds (TAM) and WSU Bridge Funding (SEB). Preliminary reports of a portion of this study were presented at the 2011 Annual meeting of the Society for Neuroscience, Washington, DC, the 2012 Annual meeting of the Pittcon Conference and Expo, Orlando, FL, the Annual Meetings of the Michigan Chapter of Society for Neuroscience, Ann Arbor and in Detroit, MI, respectively, the 2012 Annual meeting of the American Chemical Society Central Regional Meeting, Dearborn, MI, and the Detroit Section of Electrochemical Society, Ypsilanti, MI. The authors would like to thank Dr. Alana Conti for the insightful comments on the manuscript.
Conflict of interest
The authors declare no conflict of interest.