Extensive evidence suggests that 5-HT2 receptors may play a role in mental disorders including schizophrenia, depression and psychosis. In addition, several studies indicate that Gq-coupled 5-HT2A family of receptors are likely targets for the initiation of events leading to the hallucinogenic behavior elicited by lysergic acid diethylamide (LSD), (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and related drugs. However, 5-HT2A receptors couple to other G proteins in addition to Gq protein. To evaluate the role of the Gq signaling pathway in DOI-induced behaviors, we utilized two behavioral models of 5-HT2A receptor activation: induction of head-twitches by DOI, a common response to hallucinogenic drugs in rodents, and DOI elicited anxiolytic-like effects in the elevated plus maze. Experimental subjects were genetically modified mice [Gq(-/-)] in which the gene is eliminated by heterologous recombination. Gq(-/-) mice exhibited a decrease in DOI-induced head-twitches, when compared to wild-type littermates. In addition, the DOI-induced increase in anxiolytic-like behavior was abolished in Gq(-/-) mice. These results, combined with our finding that DOI-induced FOS expression in the medial prefrontal cortex was also eliminated in Gq(-/-) mice, suggests a key role for Gq protein in hallucinogenic drug effects.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03072007-170823 |
| Date | 20 April 2007 |
| Creators | Garcia, Efrain Eduardo |
| Contributors | Elaine Sanders-Bush, Craig Kennedy, Heidi Hamm, Ron emeson, Randy Blakely |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03072007-170823/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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