Effects on serotonin in rat hypothalamus of d-fenfluramine, aminorex, phentermine and fluoxetine

Tao, Rui; Fray, Anne E.; Aspley, Sue; Brammer, Richard; Heal, David J.; Auerbach, Sidney B.

doi:10.1016/s0014-2999(02)01751-x

Cited by 59 publications

(40 citation statements)

References 53 publications

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“…Fluoxetine rapidly increases extracellular 5-HT in a variety of brain areas including the hypothalamus [21,24,29,36]. Thus, acute effects of fluoxetine are consistent with 5-HT's ability to inhibit female rat sexual behavior [27,38].…”

Section: Discussionmentioning

confidence: 65%

Subchronic treatment with fluoxetine attenuates effects of acute fluoxetine on female rat sexual behavior

et al. 2008

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These experiments were designed to evaluate the hypothesis that fluoxetine-induced sexual dysfunction in female rats derived from disruption of neuroendocrine events that normally facilitate sexual behavior. If so, exogenous hormonal priming to ovariectomized rats should eliminate fluoxetine's effect. Ovariectomized rats were subchronically treated with 10 mg/kg fluoxetine or distilled/deionized water vehicle for 9 consecutive days. On the 8 th day of treatment, rats were primed with 10 μg estradiol benzoate followed 48 hr later with 500 μg progesterone. In a pretest for sexual behavior on the 10 th day, there was no difference between subchronic treatments. Sexual receptivity was again monitored 30 min after injection on the 10 th day (acute treatment) with distilled/deionized water, 10 mg/kg fluoxetine or 20 mg/kg fluoxetine. Thereafter, the female's behavior was monitored for 20 min in a male preference procedure. After the acute treatment in rats subchronically treated with water, fluoxetine (10 or 20 mg/kg) significantly reduced both lordosis frequency and quality and reduced (but not significantly) time spent with the male. In rats subchronically treated with fluoxetine, the lordosis-inhibiting effect of an acute injection with fluoxetine was significantly attenuated relative to that of the subchronically water-treated rats. In contrast to expectation, subchronic treatment with fluoxetine increased, rather than reduced, the relative time females spent near the male. Activity, as measured by center crossings, and grooming were also reduced by subchronic treatment with fluoxetine. KeywordsSSRI; sexual motivation; lordosis; subchronic IntroductionFluoxetine (Prozac®) is frequently prescribed for depression as well as for a variety of other disorders such as premenstrual dysphoria, anxiety, anorexia and bulemia which are more prevalent in females than in males [4,19,22,33]. A reported undesirable side effect of fluoxetine, as well as other selective serotonin reuptake inhibitors (SSRIs), is a high incidence of sexual dysfunction [8,15,28]. Although such sexual dysfunction occurs in both genders, more experimental emphasis has been placed on identifying the responsible mechanisms in males than in females [17]. Yet, as much as 32% of female patients may experience SSRI-*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 during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. [32]. The mechanisms responsible for such drug-induced sexual dysfunction in females have been difficult to identify,...

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Section: Discussionmentioning

confidence: 65%

Subchronic treatment with fluoxetine attenuates effects of acute fluoxetine on female rat sexual behavior

et al. 2008

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“…One of our initial predictions was that fenfluramine would deplete serotonin stores during continual application, because fenfluramine causes a peak and subsequent decline in serotonin levels over the course of tens of minutes to several hours when administered systemically (Auerbach et al 1989;Carboni and Di Chiara 1989;LaFerrere and Wurtman 1989;Rothman et al 1999;Tao et al 2002;Rothman et al 2003), and more rapidly when administered locally (Schwartz et al 1989). Refuting this prediction, the effects of fenfluramine did not decay appreciably over the course of several minutes.…”

Section: Fenfluramine and Serotonin Effects Are Similarmentioning

confidence: 92%

“…Fenfluramine is an amphetamine derivative with selectivity for the serotonergic system that in the short term increases serotonin levels in the brain but over the course of days or weeks may deplete serotonin (Rowland and Carlton 1986;Schwartz et al 1989;Baumann et al 2000;Tao et al 2002;Rothman et al 2003;Itzhak and Ali 2006). This study focuses on the effects of iontophoretically applied fenfluramine on the auditory responses of single IC neurons in a time frame of minutes.…”

Section: Introductionmentioning

confidence: 99%

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Hall

Hurley

2007

Hearing Research

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Local direct application of the neuromodulator serotonin strongly influences auditory response properties of neurons in the inferior colliculus (IC), but endogenous stores of serotonin may be released in a distinct spatial or temporal pattern. To explore this issue, the serotonin releaser fenfluramine was iontophoretically applied to extracellularly recorded neurons in the IC of the Mexican free-tailed bat (Tadarida brasiliensis). Fenfluramine mimicked the effects of serotonin on spike count and first spike latency in most neurons, and its effects could be blocked by co-application of serotonin receptor antagonists, consistent with fenfluramine-evoked serotonin release. Responses to fenfluramine did not vary during single applications or across multiple applications, suggesting that fenfluramine did not deplete serotonin stores. A predicted gradient in the effects of fenfluramine with serotonin fiber density was not observed, but neurons with fenfluramine-evoked increases in latency occurred at relatively greater recording depths compared to other neurons with similar characteristic frequencies. These findings support the conclusion that there may be spatial differences in the effects of exogenous and endogenous sources of serotonin, but that other factors such as the identities and locations of serotonin receptors are also likely to play a role in determining the dynamics of serotonergic effects.

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“…Fluoxetine rapidly increases extracellular serotonin (5-HT) by blocking the serotonin transporter (SERT) [18,48,61] and later via desensitization of 5-HT 1A somatodendritic autoreceptors in the dorsal raphe and 5-HT 1B terminal autoreceptors in some brain areas [24,44]. Disruptive effects of 5-HT on female reproduction are well recognized [37,50,56,67].…”

Section: Introductionmentioning

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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Effects on serotonin in rat hypothalamus of d-fenfluramine, aminorex, phentermine and fluoxetine

Cited by 59 publications

References 53 publications

Subchronic treatment with fluoxetine attenuates effects of acute fluoxetine on female rat sexual behavior

Subchronic treatment with fluoxetine attenuates effects of acute fluoxetine on female rat sexual behavior

The serotonin releaser fenfluramine alters the auditory responses of inferior colliculus neurons

Daily male exposure attenuates estrous cycle disruption by fluoxetine

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