The proposed research is designed to identify the CNS site(s) responsible for the inhibition of female rat sexual behavior after treatment with the 5-HT1A agonist, 8-hydroxy-2-9(di-n-propylamino) tetralin (8-OH-DPAT). Activation of somal/dendritic 5-HT1A autoreceptors by 8-OH-DPAT decreases the firing of 5-HT neurons and reduces the release of 5-HT in regions innervated by these neurons. In terminal fields, the 5-HT1A receptor exists at postsynaptic sites. Although it may also reside on presynaptic terminals, the 5-HT1A receptor does not function as the terminal autoreceptor.
The specific aims of the proposed studies are: (1) to identify the neural areas sufficient for the inhibition of female sexual behavior following treatment with 8-OH-DPAT and (2) to compare the effectiveness of this 5-HT1A agonist with that of other 5-HT1A agonists and 5-HT1B-preferring agonists. The effects of putative 5-HT1A antagonists will also be studied. Intact, regularly cycling female rats will be used and special emphasis will be placed on differentiating the postsynaptic effects of 8-OH-DPAT will then be infused intracerebrally into the medial basal hypothalamus and medial preoptic area, terminal fields that control female reproduction, and into the dorsal raphe nucleus, which contains 5-HT cell bodies. Sexual behavior will be monitored before and after infusion. These studies will provide the foundation for future investigations aimed at identifying the molecular nature and functional consequences of 5-HT1A- mediated control of sexual behavior.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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Biopsychology Study Section (BPO)
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Texas Woman's University
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Uphouse, Lynda; Hiegel, Cindy; Martinez, Giovanny et al. (2015) Repeated estradiol benzoate treatment protects against the lordosis-inhibitory effects of restraint and prevents effects of the antiprogestin, RU486. Pharmacol Biochem Behav 137:1-6
Uphouse, Lynda; Pinkston, Jonathan; Baade, Duane et al. (2015) Use of an operant paradigm for the study of antidepressant-induced sexual dysfunction. Behav Pharmacol 26:697-705
Uphouse, Lynda (2015) Dose-dependent effects of the antiprogestin, RU486, on sexual behavior of naturally cycling Fischer rats. Behav Brain Res 282:95-102
Uphouse, Lynda; Hiegel, Cindy (2014) Allopregnanolone's attenuation of the lordosis-inhibiting effects of restraint is blocked by the antiprogestin, CDB-4124. Pharmacol Biochem Behav 122:16-9
Uphouse, Lynda (2014) Pharmacology of serotonin and female sexual behavior. Pharmacol Biochem Behav 121:31-42
Uphouse, Lynda; Hiegel, Cindy; Adams, Sarah et al. (2014) Prior hormonal treatment, but not sexual experience, reduces the negative effects of restraint on female sexual behavior. Behav Brain Res 259:35-40
Uphouse, Lynda; Hiegel, Cindy (2013) An antiprogestin, CDB4124, blocks progesterone's attenuation of the negative effects of a mild stress on sexual behavior. Behav Brain Res 240:21-5
Miryala, Chandra Suma Johnson; Hiegel, Cindy; Uphouse, Lynda (2013) Comparison of female Fischer and Sprague-Dawley rats in the response to ketanserin. Pharmacol Biochem Behav 114-115:52-7
Uphouse, Lynda; Adams, Sarah; Miryala, Chandra Suma Johnson et al. (2013) RU486 blocks effects of allopregnanolone on the response to restraint stress. Pharmacol Biochem Behav 103:568-72
Miryala, Chandra Suma J; Hiegel, Cindy; Uphouse, Lynda (2013) Sprague-Dawley and Fischer female rats differ in acute effects of fluoxetine on sexual behavior. J Sex Med 10:350-61

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