Date of Award


Degree Type


Degree Name

Master of Science



Second Advisor

Dr. Rushlow

Third Advisor

Dr. R. Jane Rylett


Chronic hyperactivity of the dopaminergic system is associated with certain symptoms of schizophrenia. Our laboratory has developed a rat model of schizophrenia that involves Iesioning the developing prefrontal cortex. Lesioned animals display behaviours indicative of chronic mesolimbic dopaminergic hyperactivity consistent with other animal models of schizophrenia. Little is known concerning the molecular consequences associated with hyperdopaminergic activity in schizophrenia. The current study investigated the effects of the serine/threonine kinase Cdk5 on the phosphorylation status of DARPP- 32, a critical molecule involved in dopamine receptor-mediated signal transduction, in the nucleus accumbens in our animal model using western blotting and immunohistochemistry. Lesioned animals showed increased levels of ΔFosB, Egr-1, Cdk5, p35, p25, active Calpain-2 and phosphorylated DARPP-32 at Threonine 75 in the nucleus accumbens. The results suggest that endogenous and chronic mesolimbic dopaminergic hyperactivity may increase Cdk5 activity which can alter DARPP-32 signalling and via a feedback mechanism may interfere with dopamine receptor-mediated effects in our animal model of schizophrenia.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.