| Abstract No.: | C-C3082 |
| Country: | Canada |
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| Title: | EFFECTS OF NMDA AND DOPAMINE RECEPTOR ANTAGONISTS ON LOCOMOTOR HYPERACTIVITY IN A NOVEL PROPIONIC ACID RODENT MODEL OF AUTISM |
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| Authors/Affiliations: | 1 Jennifer Martins*; 1 Kelly Foley; 1 Roy Taylor; 1 Francis Boon; 1 Lisa Tichenoff; 1 Yalda Mohammad-Asef; 1 Peter Cain; 1 Martins Kavaliers; 1 Klaus-Peter Ossenkopp;
1 University of Western Ontario, London, ON, Canada
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| Content: | Background: Dietary or gut related factors have been proposed to alter behaviour in autism spectrum disorders (ASDs). Pharmacological agents affecting glutamatergic and dopaminergic systems have been suggested as treatments for ASDs. Propionic acid (PPA) is an enterically produced short chain fatty acid and a common food preservative which can affect a variety of processes, including cellular metabolism, gene expression, and neurotransmitter synthesis and release. Intracerebrocventricular (ICV) infusions of PPA in rats have been developed as model of ASDs.
Objective: To evaluate the role of NMDA and dopaminergic receptor antagonists on PPA induced locomotor activity in rats.
Materials and Methods: Adult male Long-Evans rats were habituated to the open-field apparatus for 3 days preceding the first treatment day. Rats were then pretreated with intraperitoneal (IP) injections of either the NMDA receptor antagonist (MK-801, 0.03 mg/kg), dopamine D2 receptor antagonist (raclopride, 0.3 mg/kg), or vehicle (phosphate buffered saline, 0.1 M) 30 min prior to intracerebroventricular (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 tested in automated open fields (Versamax) where various locomotor activity variables were quantified and measured.
Results: Rats pretreated with MK-801 prior to PPA treatment did not show significant changes in locomotor activity, with the exception of stereotypic movements. Rats pretreated with raclopride prior to PPA treatment showed a significant decrease in hyperactivity.
Conclusions: The dopamine D2 receptor systems may be involved in the PPA locomotor response in rats.
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