Open Access Dissertation
Date of Award
Scott E. Bowen
The intentional misuse of volatile solvents is a persistent public health concern. Limited self-report data suggests that chronic inhalant abusers experience withdrawal symptoms including anxiety and seizure symptoms. However, these symptoms have never been explored in a preclinical model and are not considered part of the DSM-V criteria for an Inhalant Use Disorder. For this experiment, 76 young adult male Swiss Webster mice were exposed to either 5,000 ppm toluene vapor or air (0 ppm) for 24 consecutive hours beginning on postnatal day (PND) 30. Following the 24 hour exposure, mice were allowed to recover for 3 hours before behavioral testing began. In the 1st experiment, mice were tested for handling-induced seizure activity every hour for 6 hours (and again at 24 hours). As compared to controls, toluene-abstinent animals showed persistent clonic seizure activity throughout the 6 hour period. In the 2nd experiment, mice were given a single i.p. injection of pentylenetetrazole (PTZ; 42 or 48 mg/kg) to induce seizure activity. Mice were observed for 30 min and seizure activity was scored for severity using criteria adapted from the Functional Observational Battery. As compared to air controls, toluene-abstinent mice displayed a significant increase in seizure symptoms. In the 3rd experiment, previously exposed toluene mice were re-exposed to toluene vapor for 30 min following the three hour abstinence period. Following toluene re-exposure, these mice were tested for seizure severity with 42 or 48 mg/kg PTZ. Toluene re-exposure significantly reduced the severity of the seizure response. Next, we examined anxiety-like behavior arising 24 hours following 24 hour toluene exposure. Mice were tested in the Elevated Plus Maze, Open Field Test, Light/Dark Box, and Marble Burying task at either 24 or 72 hours of abstinence. Mice 24, but not 72 hours abstinent from toluene displayed increased anxiety-like behavior. Taken together, these results suggest that toluene abstinence lowers seizure threshold in mice and increases anxiety and that toluene re-exposure ameliorates these effects. These findings provide support for clinical reports of a physical withdrawal syndrome from inhalants, which has implications for the successful diagnosis and subsequent treatment of Inhalant Use Disorders.
Callan, Sean, "A Mouse Model Of Toluene Abstinence-Induced Pathology" (2016). Wayne State University Dissertations. 1628.