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5-HT2C SEROTONIN RECEPTORS: CELLULAR LOCALIZATION AND CONTROL OF DOPAMINERGIC PATHWAYS IN THE RAT BRAIN

Alex, Katherine D
http://rave.ohiolink.edu/etdc/view?acc_num=case1164766901

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Dopamine (DA) is known to play a role in the pathology and/or treatment of schizophrenia, drug abuse and Parkinson’s disease. Serotonin (5-HT) is capable of modulating dopamine release through actions at 5-HT receptors. In particular, 5-HT2 receptor binding, and subsequent effects on DA release, may be involved in the efficacy of atypical antipsychotic drugs and recent work suggests that they may be promising targets for the treatment of depression, anxiety, obesity, and drug abuse as well. 5-HT2C receptors have been shown to tonically inhibit DA release in the striatum and the prefrontal cortex (PFC). The localization of the receptors that mediate these effects has not been studied. These data show that 5-HT2C receptors in the terminal region of the nigrostriatal pathway are, at least in part, responsible for the tonic inhibition of DA release in the striatum. In addition, data is presented that suggests that the mesocortical pathway is not modulated by 5-HT2C receptors in the terminal region. The cellular localization of 5-HT2C receptors has not been extensively studied, in part due to a lack of specific antibodies. Here, a selective 5-HT2C receptor antibody was used in immunofluorescence studies to examine the cellular localization of the 5-HT2C receptors that mediate the tonic inhibition of DA release in the brain. These studies show that 5-HT2C receptors do not colocalize with markers for parvalbumin-containing GABAergic cells in the cortex and hippocampus. Importantly 5-HT2C receptors show a high degree of colocalization with 5-HT2A receptors in these regions. 5-HT2A and 5-HT2C receptors are similar in structure and couple to the same intracellular signaling pathways upon activation. Differences in their levels of constitutive activity and desensitization in response to chronic ligand exposure have, however, been shown. Thus, by these mechanisms 5-HT2A and 5-HT2C receptors expressed in the same cortical and hippocampal pyramidal neurons may finely tune cortical efferents. The results presented here have implications for the development of new therapeutics for the treatment of diseases and disorders in which a 5-HT2 receptor-mediated manipulation of DA is beneficial.
Elizabeth Pehek (Advisor)
Biology, Neuroscience
Schizophrenia; dopamine; striatum; hippocampus; 5-HT2A; depression

Recommended Citations

Citations

  • Alex, K. D. (2007). 5-HT2C SEROTONIN RECEPTORS: CELLULAR LOCALIZATION AND CONTROL OF DOPAMINERGIC PATHWAYS IN THE RAT BRAIN [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1164766901

    APA Style (7th edition)

  • Alex, Katherine. 5-HT2C SEROTONIN RECEPTORS: CELLULAR LOCALIZATION AND CONTROL OF DOPAMINERGIC PATHWAYS IN THE RAT BRAIN. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1164766901.

    MLA Style (8th edition)

  • Alex, Katherine. "5-HT2C SEROTONIN RECEPTORS: CELLULAR LOCALIZATION AND CONTROL OF DOPAMINERGIC PATHWAYS IN THE RAT BRAIN." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1164766901

    Chicago Manual of Style (17th edition)

case1164766901
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© 2006, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.