A Mouse Model Of Toluene Abstinence-Induced Pathology

A MOUSE MODEL OF TOLUENE ABSTINENCE-INDUCED PATHOLOGYbySean P. CallanDecember 2016Advisor: Dr. Scott BowenMajor: PsychologyDegree: Doctor of PhilosophyThe intentional misuse of volatile solvents is a persistent public health concern. Limitedself-report data suggests that chronic inhalant abusers experience withdrawal symptoms includinganxiety and seizure symptoms. However, these symptoms have never been explored in apreclinical 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 ppmtoluene 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 testingbegan. In the 1st experiment, mice were tested for handling-induced seizure activity every hour for6 hours (and again at 24 hours). As compared to controls, toluene-abstinent animals showedpersistent clonic seizure activity throughout the 6 hour period. In the 2nd experiment, mice weregiven a single i.p. injection of pentylenetetrazol (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 adaptedfrom the Functional Observational Battery. As compared to air controls, toluene-abstinent micedisplayed a significant increase in seizure symptoms. In the 3rd experiment, previously exposedtoluene mice were re-exposed to toluene vapor for 30 min following the three hour abstinence