Date of Award
2008
Degree Type
Thesis
Degree Name
Master of Science
Program
Neuroscience
Supervisor
Dr. Derrick MacFabe
Second Advisor
Dr. Peter Ossenkopp
Third Advisor
Dr. Martin Kavaliers
Abstract
Propionic acid (PPA) is an enterically produced short chain fatty acid and also a common food preservative. PPA can affect a variety of processes including cellular metabolism, gene expression, and neurotransmitter synthesis and release. Intracerebrocventricular (ICV) infusions of PPA in adult Long-Evans rats have been used to model ASDs. Pharmacological agents affecting glutamatergic and dopaminergic systems have been suggested as treatments for ASDs. In the present studies, adult male Long-Evans rats were habituated for 3 days in the locomotor activity system. Rats were then pretreated with intraperitoneal (IP) injections of either the NMDA antagonist MK- 801 (0.03 mg/kg), the dopamine D2 receptor antagonist raclopride (0.3 mg/kg), the dopamine Dl receptor antagonist SCH 23390 (0.25 mg/kg), or vehicle (phosphate buffered saline, 0.1 M) 30 min prior to ICV infusions of PPA (0.25 M buffered to pH 7.5) or vehicle twice daily for 4 consecutive days. After the second PPA infusion on each treatment day, animals were individually placed into automated open fields (Versamax) where various locomotor activity variables were quantified and then analyzed. Rats pretreated with MK-801 prior to PPA infusions did not display a decrease in locomotor activity. However, rats pretreated with raclopride or SCH 23390 prior to PPA treatment exhibited a decrease in hyperactivity. The dopamine D1 and D2 receptor systems may play a role in the PPA enhanced locomotor response in rats.
Recommended Citation
Martins, Jennifer N., "THE EFFECTS OF NMDA AND DOPAMINE ANTAGONISTS IN A NOVEL PROPIONIC ACID RODENT MODEL OF AUTISM" (2008). Digitized Theses. 4525.
https://ir.lib.uwo.ca/digitizedtheses/4525