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Dissertation
Functional consequences of 5-HT₂A receptor modulation in the rabbit forebrain
Doctor of Philosophy (Ph.D.), Drexel University
May 2004
DOI:
https://doi.org/10.17918/00000645
Abstract
Motor movement, a fundamental component of behavior, is the principle extrinsic action of the brain. Serotonergic (5-HT) neurotransmitter system plays an important role in modulating neuronal excitability and in turn modulating motor behavior. This thesis systematically investigated the effects of modulating Serotonin2A (5-HT2A) receptor density in the rabbit forebrain on elicitation of motor behavior. First, an in vivo model for the activation of 5-HT2A receptors in the rabbit was developed by examining the behavioral effects of systemically administering 5-HT2A/2C receptor agonist DOI and using selective 5-HT2A and 5-HT2C receptor antagonists. This study demonstrated that DOI induced two distinct and dose-dependent behaviors in the rabbit, head bobs and body shakes and that head bobs were 5-HT2A receptor-mediated and body shakes were 5-HT2C receptor-mediated. Second, these motor behaviors were further characterized by investigating whether they were centrally mediated using peripheral 5-HT2A/2C receptor antagonist and direct infusions of DOI into the lateral ventricle. These studies concluded that 5-HT2A receptors mediating head bobs were located in the forebrain near the lateral ventricle whereas 5-HT2C receptors mediating the body shakes appear to be located at different central sites as well as in the periphery. Third, the relationship between the 5-HT2A receptor density in the frontal cortex and motor behavior was investigated using 5-HT 2A/2C receptor antagonists BOL and MDL 11939. These studies established a highly significant relationship between the number of 5-HT2A receptors in the frontal cortex and the number of head bobs produced by activation of these receptors. Finally, the role of dorsal hippocampus in 5-HT2A receptor-mediated behavior was examined. This was done by examining whether intra-hippocampal administration of DOI would elicit head bobs and whether this elicitation would be modified by altering 5-HT2A receptor density. These studies indicated that 5-HT2A receptors located in the CAS field of the dorsal hippocampus mediate head bobs and that this mediation is functionally related to receptor density. In conclusion, this thesis is the first to systematically correlate the density of 5-HT2A receptors in the frontal cortex with elicitation of motor movements and is the first to demonstrate the role of the hippocampal 5-HT2A receptors in motor behavior.
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Details
- Title
- Functional consequences of 5-HT₂A receptor modulation in the rabbit forebrain
- Creators
- Kuldip D. Dave
- Contributors
- Vincent J. Aloyo (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 94 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991014970195404721