Serotonin Inhibits Luteinizing Hormone Release via 5-HT1A Receptors in the Zona incerta of Ovariectomised, Anaesthetised Rats Primed with Steroids

Siddiqui, Anwar Ali; Kotecha, Krishna; Salicioni, Ana-Maria; Kalia, Veena; Murray, Joanne F.; Wilson, Catherine

doi:10.1159/000054596

Cited by 17 publications

(9 citation statements)

References 42 publications

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“…Disruptive effects of 5-HT on female reproduction are well recognized [37,50,56,67]. In addition, several of the effects of fluoxetine (in particular, reduced food intake [3,4,6,23] and activation of the hypothalamic-pituitary-adrenal (HPA) axis [54,68]) might be anticipated to substantially alter the neuroendocrine system and thereby influence the female's reproductive cycle [2,7,26,27,29,53,69].…”

Section: Nih-pa Author Manuscriptmentioning

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: Nih-pa Author Manuscriptmentioning

confidence: 99%

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Sarkar

Hiegel

Maswood

et al. 2008

Behavioural Brain Research

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“…The possible inhibitory effect of orexin in this model was noted by injecting orexin centrally approximately 2 h after the progesterone and thus approximately 2 h before the expected time of the LH surge. These experimental models are well established and have been previously used to investigate the role of melanin-concentrating hormone, dopamine, and 5-hydroxytryptamine (5HT) on LH release (4,5,25).…”

Section: In Vivo Experimentsmentioning

confidence: 99%

“…Procedures. All rats were anesthetized with Saffan (see above) and placed on a heated electric pad to maintain body temperature (25). A blood sample (0.2 ml) was taken from the tail vein just before the intrahypothalamic treatment, 50 -51 h after the EB priming; this means that in groups treated with EB plus progesterone, the intrahypothalamic injection was given 2-3 h after the progesterone and thus approximately 1-2 h before the expected LH surge.…”

Section: In Vivo Experimentsmentioning

confidence: 99%

Central Orexin A Has Site-Specific Effects on Luteinizing Hormone Release in Female Rats

et al. 2003

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Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.

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“…Saffan anaesthesia was employed (alphaxalone 0.9%, alphadolone acetate 0.3%: Veterinary Supplies, Stoke‐on‐Trent, UK) at 3 ml/kg i.p. Since this anaesthetic does not block the steroid‐induced surge‐like increase in LH release, it allows the investigation of the effects of a putative inhibitory agent on the occurrence of this surge‐like release (43). Compounds were injected into the CNS via a 10 µl syringe (Hamilton, Carnforth, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples were collected from the tail vein, just before the central injection (0 min) and then postinjection at either 10‐ or 20‐min intervals for a 2‐h period (after OB alone), or at 30‐min intervals for a 3‐h period (after OB plus P). The rats were kept on a heated pad to maintain body temperature and to facilitate blood collection by inducing vasodilatation (43).…”

Section: Methodsmentioning

confidence: 99%

Evidence for a Stimulatory Action of Melanin‐Concentrating Hormone on Luteinising Hormone Release Involving MCH1 and Melanocortin‐5 Receptors

Murray

Hahn

Kennedy

et al. 2005

J Neuroendocrinology

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The present series of studies aimed to further our understanding of the role of melanin-concentrating hormone (MCH) neurones in the central regulation of luteinising hormone (LH) release in the female rat. LH release was stimulated when MCH was injected bilaterally into the rostral preoptic area (rPOA) or medial preoptic area (mPOA), but not when injected into the zona incerta (ZI), of oestrogen-primed ovariectomised rats. In rats that were steroid-primed to generate a surge-like release of LH, MCH administration into the ZI blocked this rise in LH release: no such effect occurred when MCH was injected into the rPOA or mPOA. In vitro, MCH stimulated gonadotrophin-releasing hormone (GnRH) release from hypothalamic explants. Double-label immunohistochemistry showed GnRH-immunoreactive neurones in the vicinity of and intermingled with immunoreactive MCH processes. MCH is the endogenous ligand of the MCH type 1 receptor (MCH1-R). Previously, we have shown a role for melanocortin-5 receptors (MC5-R) in the stimulatory action of MCH, so we next investigated the involvement of both MCH1-R and/or MC5-R in mediating the actions of MCH on GnRH and hence LH release. The stimulatory action of MCH in the rPOA was inhibited by administration of antagonists for either MCH1-R or MC5-R. However, in the mPOA, the action of MCH was blocked only by the MC5-R antagonist. LH release was stimulated by an agonist for MC5-R injected into the rPOA or mPOA; this was blocked by the MC5-R antagonist but not the MCH1-R antagonist. These results indicate that both MCH1-R and MC5-R are involved in the central control of LH release by MCH.

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Serotonin Inhibits Luteinizing Hormone Release via 5-HT1A Receptors in the Zona incerta of Ovariectomised, Anaesthetised Rats Primed with Steroids

Cited by 17 publications

References 42 publications

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Daily male exposure attenuates estrous cycle disruption by fluoxetine

Central Orexin A Has Site-Specific Effects on Luteinizing Hormone Release in Female Rats

Evidence for a Stimulatory Action of Melanin‐Concentrating Hormone on Luteinising Hormone Release Involving MCH1 and Melanocortin‐5 Receptors

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