<p> Schizophrenia is treated with haloperidol, an antipsychotic drug. Although highly effective in treating the positive symptoms of this disease, extrapyramidal side effects also accompany haloperidol treatment, including parkinsonism. Previous investigations revealed that dopamine receptor blockade by haloperidol was not temporally correlated with the appearance of parkinsonian side effects, which begin approximately 3 weeks after haloperidol treatment. In fact, by using tyrosine hydroxylase as a marker for dopamine, TH-immunoreactivity was significantly decreased 5 minutes after haloperidol administration and further downregulation was seen after 10 minutes. Microglial activation has also been implicated in Parkinson's disease models. Haloperidol also induces maximal microglial activation at 5 minutes after administration, with activation increasing by 2 minutes. In this respect, microglial activation may precede TH downregulation, thereby mediating the downregulation. In order to test this possibility, minocycline, a microglial inhibitor, was administered to Sprague-Dawley rats. Minocycline successfully inhibited microglial activation and showed partial protection over TH levels. Caffeine and nicotine have also been implicated as neuroprotective agents in Parkinson's disease. Epidemiological evidence has indicated that both caffeine and nicotine protect against Parkinson's disease. Therefore, caffeine and nicotine were independently tested and found to both prevent TH downregulation and inhibit microglial activation. Overall, microglial activation has been found to correlate with TH downregulation induced by haloperidol. Minocycline, nicotine and caffeine have all been found to inhibit microglial activation, preventing neurotoxicity associated with haloperidol administration. </p> / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/22296 |
| Date | 08 1900 |
| Creators | Lagrou, Lisa |
| Contributors | Mazurek, Michael, Medical Sciences (Neuroscience and Behavioral Science) |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
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