Date of Award

2010

Degree Type

Dissertation

Degree Name

Master of Science

Program

Neuroscience

Supervisor

Dr. Klaus-Peter Ossenkopp

Second Advisor

Dr. Martin Kavaliers

Third Advisor

Dr. Derrick F. MacFabe

Abstract

Autism spectrum disorders (ASDs) are characterized by altered motor activity, restricted interests and social impairment, and are four times more prevalent in males. Co-morbidities such as anxiety disorder, sickness behaviour and gastrointestinal symptoms are present in a subset of patients. Propionic acid (PPA) is a short-chain fatty acid and end-product of enteric bacteria that has been implicated in autism symptoms. Experiment one examined the effects of 14 days of twice daily intraperitoneal (IP) injections of PPA (500mg/kg, 0.26 M, pH 7.5) on locomotor activity and social interaction in juvenile male and female Long-Evans rats. Male and female PPA treated rats exhibited hypoactivity and increased anxiety-related behaviours, as indexed by decreased rearing and stereotypy, and increased thigmotaxis. Only the male PPA treated rats showed social impairment as evidenced by decreased percentage of time in physical contact. These findings suggest that PPA can alter social behavior in a sex- specific manner. Experiment two investigated the effects of IP injections of PPA (500mg/kg, 0.26 M, pH 7.5) in juvenile male rats in a place & taste avoidance paradigm in order to investigate the induction of aversive internal cues by PPA. Over 12 conditioning days rats received alternating IP injections of PPA (or PPA with 2 % saccharin) & vehicle (phosphate buffered saline; 0.15 M) in separate contexts. On a drug-free test day, PPA treated rats did not exhibit a significant avoidance of the treatment-paired chamber, nor did PPA-saccharin treated rats avoid 0.2 % saccharin water. However, PPA rats spent a greater percentage of time rearing in the treatment- paired chamber, a putative index of escape behavior. These results suggest that IP injections of PPA may induce some aversive internal cues. Together, these experiments offer further support towards propionic acid administration as an animal model of autism.

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