5-HT2C receptor involvement in female rat lordosis behavior

Wolf, Amy; Caldarola-Pastuszka, Marjay; DeLashaw, Mini; Uphouse, Lynda

doi:10.1016/s0006-8993(99)01159-2

Cited by 29 publications

(25 citation statements)

References 15 publications

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“…In addition to fluoxetine's modulation of extracellular serotonin, fluoxetine also antagonizes 5-HT 2C and 5-HT 3 receptors [9][10][11]22,45], both of which have been positively implicated in the control of female rat sexual behavior [33,34,70,71]. Finally, fluoxetine enhances the conversion of progesterone to a variety of metabolites other than 3α-5α-THP.…”

Section: Discussionmentioning

confidence: 99%

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Sarkar

Hiegel

Maswood

et al. 2008

Behavioural Brain Research

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Fluoxetine (Prozac®) produces sexual dysfunction in a substantial number of patients. In the few animal studies designed to address this sexual dysfunction in females, data have been inconsistent. Some investigators report that the drug disrupts sexual behavior without affecting the estrous cycle while we have reported robust effects of fluoxetine on the estrous cycle. The current studies were designed to initiate examination of procedural differences that may account for these contradictory outcomes. In the first experiment, intact, regularly cycling female rats were injected daily for 10 days with 10 mg/kg fluoxetine (intraperitoneally) or vehicle. Male-exposed, fluoxetine-or vehicle-treated rats were housed in a room with males and placed for 5 min/day into a male's cage. Other fluoxetinetreated females were housed in a room separate from males. In the second experiment, this protocol was repeated for 20 days and an additional group of females were exposed to male bedding for 5 min/day. Without male exposure, fluoxetine rapidly disrupted vaginal estrus and sexual receptivity so that approximately 50% of the rats failed to show vaginal estrus during the first 5 days; and the majority of the rats had a blocked cycle by 10 days of treatment. With male exposure, these reproductive effects were attenuated. The majority of rats cycled normally during the first 5 days of treatment and more than half cycled throughout the experiment. Loss of behavioral receptivity occurred even when normal estrous cyclicity was present. Although exposure to the male's bedding may have delayed the onset of estrous cycle disruption, five min daily exposure to a male's bedding did not prevent the disruptive effects of fluoxetine. These findings are consistent with evidence that fluoxetine's effect on female sexual dysfunction may result, in part, from the drugs' disruption of the hypothalamic-pituitary-gonadal axis. However, the data also evidence dissociation between the effects of fluoxetine on vaginal and behavioral estrus. These findings may also explain why different laboratories have reported the presence or absence of estrous cycle disturbances following daily treatment with fluoxetine. KeywordsSSRIs; intact rats; sexual behavior; pheromones; progesterone; estrus INTRODUCTIONSelective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac®), are effective in the treatment of depression [32,66] but produce sexual dysfunction in a substantial number of patients [12,19,38,39,55,59]. Although the high prevalence of SSRI-induced sexual *Corresponding author: Department of Biology, Texas Woman's University, Denton, TX 76204, Phone: 940-898-2356, FAX: 940-898-2382.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that durin...

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Section: Discussionmentioning

confidence: 99%

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Sarkar

Hiegel

Maswood

et al. 2008

Behavioural Brain Research

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“…Some 5-HT receptors have been reported to play a facilitative role in regulating lordosis behavior, because lordosis is enhanced by treatment with a 5-HT 2A/2C receptor agonist (Wolf et al , 1998;Wolf et al , 1999) and is suppressed by a 5-HT 2A/2C antagonist (Wolf et al , 1998;Wolf et al , 1999) or a 5-HT 3 receptor antagonist (Maswood et al , 1997;Maswood et al , 1998). If 5-HT 7 receptor is involved in the lordosis-facilitating mechanisms of the serotonergic neuron, lordosis is expected to increase by treatment with (+)8-OH-DPAT.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, since lordosis is facilitated by treatment with the 5-HT 2A/2C receptor agonist, DOI, and conversely, is inhibited by the antagonist, ketanserin (Wolf et al , 1998;Wolf et al , 1999), 5-HT 2A/2C receptor plays an important role in the lordosis facilitating mechanism. Moreover, treatment with the 5-HT 3 receptor antagonist, tropisetron, decreased lordosis (Maswood et al , 1997;Maswood et al , 1998).…”

Section: Introductionmentioning

confidence: 96%

Effects of Highly or Relatively Selective 5-HT_1AReceptor Agonists on Lordosis in Female Rats

Kishitake¹,

Yamanouchi²

2003

Zoological Science

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“…Within the VMN, we have suggested that DOI's facilitation of lordosis behavior involves 5-HT 2C rather than 5-HT 2A receptors [45], although other investigators have emphasized the 5-HT 2A rather than the 5-HT 2C [9]. While it may be reasonable to assume involvement of 5-HT 2C receptors in the current study, the receptor subtype responsible for DOI's attenuation of the effects of 5-HT 1A receptors has not yet been established.…”

Section: Discussionmentioning

confidence: 99%

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

Selvamani

Lincoln

Uphouse

2007

Behavioural Brain Research

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Ovariectomized rats with bilateral cannulae near the ventromedial nucleus of the hypothalamus were hormonally primed with 10μg estradiol benzoate and 500μg progesterone. Sexually receptive females were infused bilaterally with 200 ng of the 5-HT 1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), or with a combination of 200 ng 8-OH-DPAT and 2000 ng of the 5-HT 2 receptor agonist, (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCl (DOI). 8-OH-DPAT inhibited lordosis behavior and DOI reduced this inhibition. However, if females were preinfused with the PKC inhibitor, bisindolymaleimide I hydrochloride (BIM), DOI's effect was eliminated. BIM's attenuation of the effects of DOI was time-dependent. When BIM was infused 90 min, but not 30 min, before the 5-HT receptor agonists, BIM eliminated DOI's protection against the lordosisinhibiting effects of 8-OH-DPAT. A concentration of BIM as low as 10 −5 nmol in a 0.5μl infusion volume was effective and there was little evidence of dose responsivity between 10 −5 and 10 −1 nmol of BIM. In contrast, prior infusion with vehicle or with 10 −7 nmol BIM had no impact on the female's response to the 5-HT receptor agonists. These findings allow the suggestion that DOI's ability to increase PKC may be responsible for attenuation of the effects of 8-OH-DPAT on lordosis behavior. KeywordsPKC inhibitor; 5-HT 1A receptors; 5-HT 2 receptors; ovariectomized; sexual behavior IntroductionWithin the ventromedial nucleus of the hypothalamus (VMN), serotonin (5-HT) modulates female rat sexual behavior by acting on multiple 5-HT receptors [39]. Lordosis behavior, a supraspinal estrogen-dependent reflex of sexually receptive females [29], is inhibited by 5-HT 1A receptor agonists and facilitated by 5-HT 2 receptor agonists and their coactivation attenuates the lordosis-inhibitory effects of 5-HT 1A receptor agonists [39]. We have proposed that this 5-HT 1A /5-HT 2 receptor interaction enables the female to fine-tune her behavior so that it is most adaptive to environmental conditions [42]. However, the mechanisms for this interaction are not known.

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5-HT2C receptor involvement in female rat lordosis behavior

Cited by 29 publications

References 15 publications

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Effects of Highly or Relatively Selective 5-HT_1AReceptor Agonists on Lordosis in Female Rats

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

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5-HT2C receptor involvement in female rat lordosis behavior

Cited by 29 publications

References 15 publications

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Effects of Highly or Relatively Selective 5-HT1AReceptor Agonists on Lordosis in Female Rats

The PKC inhibitor, bisindolymaleimide, blocks DOI's attenuation of the effects of 8-OH-DPAT on female rat lordosis behavior

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Effects of Highly or Relatively Selective 5-HT_1AReceptor Agonists on Lordosis in Female Rats