| dc.contributor.author | Chase, Teena D. | en_US |
| dc.date.accessioned | 2014-10-21T12:36:37Z | |
| dc.date.available | 2006 | |
| dc.date.issued | 2006 | en_US |
| dc.identifier.other | AAINR16712 | en_US |
| dc.identifier.uri | http://hdl.handle.net/10222/54802 | |
| dc.description | Many children are treated with Ritalin (methylphenidate; MPH) over long periods of time, during critical periods of neural development. The purpose of this Thesis was to investigate the effects of acute and chronic MPH exposure on gene expression in the developing rat brain. Of particular interest were the immediate early genes cfos, fosb, and arc, and the neurotrophin bdnf, which encode proteins implicated in developmental neuroplasticity. A critical goal of this Thesis was to develop a clinically relevant method for administering oral MPH to prepubertal rats at an age that corresponds to the time-period of therapeutic treatment of children. Using a rat model, I hypothesized that changes in gene expression would be a first step to uncovering the mechanisms of MPH action in the developing brain. | en_US |
| dc.description | Acute MPH treatment stimulated cFOS immunoreactivity (ir) and mRNA expression in the prepubertal rat striatum, and this effect was desensitized by repeated MPH treatment (daily; 14 days; s.c.). A similar induction and attenuation of ARC-ir and mRNA expression was observed in the striatum. In contrast, acute and chronic MPH treatment had little effect on striatal bdnf mRNA levels. The inhibitory effect of chronic MPH on the normal cfos and arc response persisted into adulthood. In contrast to the inhibitory effect on striatal cFOS-ir, repeated MPH elevated FOSB-ir in prepubertal rats. However, fosB and DeltafosB mRNA appeared to be inhibited by chronic MPH treatment. MPH also induced expression of cFOS or FOSB-ir in several extra-striatal regions of the immature brain including the cingulate/frontal and piriform cortices. In the adult rat brain, MPH altered striatal cFOS, ARC and FOSB-ir although not to the extent observed in the young brain. Finally, a novel technique was developed to treat young rats with oral MPH. Oral MPH effectively elevated levels of striatal cfos, fosB and arc expression in the immature rat brain, and chronic oral MPH attenuated cfos expression while elevating fosB expression. | en_US |
| dc.description | These findings have implications for the long-term use of MPH to treat children with ADHD. Through regulation of cfos, fosB and arc, MPH may induce long-lasting changes in neuroplasticity, synaptic structure and function. | en_US |
| dc.description | Thesis (Ph.D.)--Dalhousie University (Canada), 2006. | en_US |
| dc.language | eng | en_US |
| dc.publisher | Dalhousie University | en_US |
| dc.publisher | | en_US |
| dc.subject | Biology, Molecular. | en_US |
| dc.subject | Biology, Neuroscience. | en_US |
| dc.subject | Biology, Physiology. | en_US |
| dc.title | The effects of methylphenidate on gene expression in the developing rat brain. | en_US |
| dc.type | text | en_US |
| dc.contributor.degree | Ph.D. | en_US |
