Date of Award
2007
Degree Type
Thesis
Degree Name
Master of Science
Program
Neuroscience
Supervisor
Dr. Nagalingam Rajakumar
Abstract
Schizophrenia is characterized by chronic dopaminergic hyperactivity and increased release of dopamine at mesolimbic terminals. Our lab has developed a putative animalmodelofschizophreniabyablatingthedevelopingprefrontalcortexinrats. As adults, these animals display behavioral features representing chronic mesolimbic dopaminergic hyperactivity. The role of increased levels of cyclin-dependent kinase 5 (cdk5) may play in mesolimbic dopamine release was investigated in adult rats that receivedneonatalprefrontalcorticalablation. Resultsshowedincreasedlevelsofcdk5 protein in dopamine neurons in lesioned rats, and revealed increased levels of phosphorylated dynamin-1 at serine 774 and 778, targets of cdk5, in mesolimbic dopamine neurons suggesting increased cdk5 activity. Behavioral studies have shown increased locomotor response to stress, methamphetamine or apomorphine in lesioned rats compared to control animals. The intra-accumbens infusions of roscovitine, an inhibitor of cdk5, reduced both stress- and methamphetamine-induced locomotor behavior, while increased apomorphine-induced locomotor responses in these rats. Results suggest that increased cdk5 activity in mesolimbic dopamine neurons may facilitate increased mesolimbic dopaminergic activity.
Recommended Citation
Sathanantham, Kesavan, "Cdk5-dependent augmentation of dopamine release at mesolimbic terminals may contribute to the enhanced dopaminergic activity in schizophrenia" (2007). Digitized Theses. 4948.
https://ir.lib.uwo.ca/digitizedtheses/4948