International Meeting for Autism Research (London, May 15-17, 2008): Intraventricular Propionic Acid - Induced Hyperactivity: Role of NMDA and Dopamine Receptor Antagonists in a Novel Propionic Acid Rodent Model of Autism

Intraventricular Propionic Acid - Induced Hyperactivity: Role of NMDA and Dopamine Receptor Antagonists in a Novel Propionic Acid Rodent Model of Autism

Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
J. Martins , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
K. A. Foley , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
J. E. Hoffman , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
F. Boon , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
L. J. Tichenoff , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
A. R. Taylor , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
Y. Mohammad-Asef , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
D. P. Cain , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
M. Kavaliers , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
K. -. P. Ossenkopp , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
D. F. MacFabe , The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
Background: Dietary or gut related factors have been proposed to alter behaviour in autism spectrum disorders (ASDs).  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 rats have been used to model ASDs.  Pharmacological agents affecting glutamatergic and dopaminergic systems have been suggested as treatments for ASDs.        
Objectives: To evaluate the role of NMDA and dopaminergic receptor antagonists on PPA induced locomotor activity increases in rats.
Methods: 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 receptor antagonist MK-801 (0.03 mg/kg), the dopamine D2 receptor antagonist raclopride (0.3 mg/kg), or vehicle (phosphate buffered saline, 0.1 M) 30 min prior to ICV infusions of PPA (500 µg/µL 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. 
Results: Rats pretreated with MK-801 prior to PPA treatment did not alter locomotor activity, with the exception of stereotypic movements.  However, preliminary results suggested rats pretreated with raclopride prior to PPA treatment exhibited a decrease in hyperactivity.   
Conclusions: The dopamine D2 receptor systems may play a role in the PPA enhanced locomotor response in rats.