The most common treatment strategy for adolescents with attention deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) is combined methylphenidate (MPH) and fluoxetine (FLX). This has raised concerns because combined MPH+FLX treatment may have pharmacodynamic properties similar to cocaine, potentially increasing drug abuse liability. Chronic exposure to cocaine results in very distinct patterns of gene expression and it is important to know if combined MPH+FLX results in the same pattern of expression. To this end, adult (PD 70-84) and adolescent (postnatal days [PD] 21-34) male mice were exposed to vehicle, MPH, FLX, MPH+FLX, or cocaine treatment twice daily for 15 days. Mice were sacrificed 24 h or 2 months after the last drug injection to assess the effect of drug treatment on the extracellular signal-regulated protein kinse-1/2 (ERK) pathway within the ventral tegmental area (VTA), a brain region known to be key in mediating the reinforcing properties of reward. Sensitivity for nicotine (0.07 mg/kg) was assessed as measured by the place-conditioning paradigm (CPP) 24 hours and 2 months after adolescent drug pretreatment. MPH+FLX and cocaine exposure during adolescence increased mRNA expression of ERK2 and its downstream targets cAMP response element-binding protein (CREB), c-Fos, and early growth response protein (Zif268), and also increased protein phosphorylation ERK2 and CREB 2 months after drug exposure when compared to vehicle-treated controls. Adolescent drug pretreatment increased preference for nicotine when tested in adulthood. These results indicate that combined MPH+FLX and cocaine exposure during adolescence have a similar profile: disrupt the ERK pathway, a signaling cascade implicated in motivation and mood regulation, within the VTA, while increasing sensitivity for nicotine in adulthood. / A Thesis submitted to the Department of Psychology in partial fulfillment of the requirements for the degree of
Master of Arts. / Summer Semester, 2013. / June 21, 2013. / Includes bibliographical references. / Carlos A. Bolaños-Guzmán, Professor Directing Thesis; Janet Kistner, Committee Member; Frank Johnson, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_253310 |
| Contributors | Alcantara, Lyonna F. (authoraut), Bolaños-Guzmán, Carlos A. (professor directing thesis), Kistner, Janet (committee member), Johnson, Frank (committee member), Department of Psychology (degree granting department), Florida State University (degree granting institution) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource, computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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