Date of Award
Master of Science
Dr. Klaus-Peter Ossenkopp
Autism spectrum disorders (ASD) are a cluster of neurodevelopmental disorders characterized by abnormal social interactions, communication deficits, and repetitive and restricted behaviours. Propionic acid (PPA), a component of fatty acid metabolism, is endogenous to the human body, produced by enteric gut bacteria, and crosses both the gut-blood and the blood-brain barrier. Previous research has demonstrated that repeated intracerebroventricular (ICV) infusions of PPA in adult rats produce behavioural and neuropathological changes similar to those seen in ASD patients. The current studies further characterized this animal model, focusing on repetitive and perseverative behaviours, through the use of the hole-board apparatus. Adult male Long-Evans rats received ICV infusions twice a day, 4 hours apart, of high-dose PPA (0.26 M), low-dose PPA (0.052 M), or phosphate buffered saline (PBS) for 7 consecutive days. Locomotor activity and nose poke behaviour were recorded daily in an automated open field apparatus (Versamax) equipped with a 16 well hole-board for 30 minutes immediately after the second infusion. In the first study, all wells remained empty. PPA treatment increased locomotor and nose poking behaviour in a dose-dependent manner. In the second study, relevant olfactory stimuli (i.e., clean and soiled bedding) was placed within the wells as a means of measuring perseverative behaviour. Both high- and low- dose PPA animals failed to modify their nose poking patterns, suggestive of perseverative behaviour. This work further supports the face validity of the PPA rodent model of ASD by demonstrating that repetitive and perseverative behaviours, core symptoms of autism, occur within PPA infused rats.
Meeking, Melissa M., "INTRACEREBROVENTRICULAR PROPIONIC ACID INCREASES LOCOMOTOR ACTIVITY AND NOSE POKES IN RATS TESTED IN AN AUTOMATED HOLE-BOARD APPARATUS: DOSE RESPONSE EFFECTS IN AN ANIMAL MODEL OF AUTISM SPECTRUM DISORDERS" (2011). Digitized Theses. 3438.