Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed disorder in children. Methylphenidate (MPH) or Ritalin, is a psychostimulant widely prescribed to treat ADHD from childhood to adulthood. Although patients take MPH for years, studies investigating long-term MPH use are lacking. Additionally, abuse of MPH is a growing problem in young adults. MPH blocks dopamine and norepinephrine transporters, which extends these neurotransmitters’ actions by preventing their reuptake from the cleft. Previous research has shown that long-term exposure to MPH causes dopamine-releasing neurons in the nigrostriatal pathway to become more susceptible to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, the mechanism by which MPH sensitizes neurons to MPTP in a female model was investigated. The hypothesis was that oxidation of excess dopamine to a quinone causes neurons within this pathway to become more susceptible to MPTP. This dopamine quinone may be conjugated by the antioxidant glutathione (GSH); however, with an excess of dopamine and therefore quinones, GSH levels will become depleted. Without protection from GSH, quinones may lead to production of highly reactive free radicals, precipitating cell death. Estrogen is thought to be neuroprotective to MPTP, so it was further hypothesized that anestrus (low estrogen) females will show more dopamine cell loss, more quinone production, and more GSH depletion than proestrus (high estrogen) females. To test this hypothesis, MPTP-resistant adolescent female Swiss-Webster mice were divided into 3 treatment groups: saline (control), 1 mg/kg MPH (therapeutic dose), or 10 mg/kg (abusive dose). Within each group, mice were divided into proestrus and anestrus subgroups. All mice were injected twice daily with MPH or saline. After 12 weeks of injections followed by a 7 day washout period, half of each grouping received MPTP injections (4 x 20 mg/kg every 2 hours), while the other half received 4 injections of sterile saline. Mice were sacrificed either 3 or 7 days post-MPTP or saline injection. The substantia nigra and striatum of the nigrostriatal pathway that are affected by Parkinson’s disease were collected. Proestrus females in the saline group showed a significant (pmore dopamine quinone production (*p
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:asrf-1774 |
| Date | 18 March 2021 |
| Creators | Phillips, Kaitlyn, Pond, Brooks B, Oakes, Hannah, McWethy, David R |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | Appalachian Student Research Forum |
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