Master of Science (MSc)
Faculty of Science
Dr. Bruce E McKay
Toluene is a volatile solvent found in many household products and when intentionally inhaled results in intoxication. In rats, acute inhalation of toluene results in sedation and neurological impairments, with marked increases in ambulation and vertical behaviour during the recovery period. Previous in vitro research has shown that toluene may exert its effects by inhibiting NMDA receptors, and / or by activating GABAA receptors. To test whether modulation of these receptors are also implicated in the changes in motor behaviour and neurological impairments resulting from toluene vapour inhalation, rats were injected with the NMDA receptor co-agonist D-serine (1000 mg/kg i.p.), the GABAA antagonist picrotoxin (0.05 mg/kg i.p.), or saline, and then received whole-body exposures to either 15 or 30 min of an abuse-relevant concentration of toluene vapour (~ 5000 ppm). Open field behaviours including locomotion, rearing, and grooming as well as neurological impairments were quantified before and after toluene vapour inhalation. The results indicate that D-serine increases the speed of recovery from ambulatory and neurological impairments following 30 min (but not 15 min) exposure to toluene, suggesting an important role for NMDA receptors in the behavioural impairments induced by prolonged toluene intoxication. In contrast, picrotoxin did not affect recovery from toluene intoxication, suggesting that GABAA receptors are not implicated in the effects of toluene vapor inhalation, at least at the dose of toluene and exposure durations tested.
Samuel-Herter, Susan R., "RECOVERY FROM ACUTE TOLUENE INTOXICATION IS FACILITATED BY THE NMDA RECEPTOR CO-AGONIST D-SERINE, BUT NOT THE GABAA RECEPTOR ANTAGONIST PICROTOXIN" (2014). Theses and Dissertations (Comprehensive). 1677.