Estrous cycle modulation of extracellular serotonin in mediobasal hypothalamus: role of the serotonin transporter and terminal autoreceptors

Maswood, Sharmin; Truitt, William A.; Hotema, Martha; Caldarola-Pastuszka, Marjay; Uphouse, Lynda

doi:10.1016/s0006-8993(99)01439-0

Cited by 103 publications

(52 citation statements)

References 45 publications

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“…Female rats showed lower baseline hypothalamic 5-HT levels and a reduced response to paroxetine or fenfluramine during estrous than males (Gundlah et al, 1998). Dramatic sex differences were also shown in the regulation of 5-HT efflux in the hypothalamus of rats after local perfusion of the nonselective 5-HT 1B/1D receptor antagonist methiothepin (Maswood et al, 1999). Female rats showed a significant increase in 5-HT efflux after methiothepin, whereas methiothepin did not change extracellular 5-HT levels of male rats.…”

Section: -Ht Microdialysis Measurementmentioning

confidence: 88%

“…For example, blockade of 5-HT 1A autoreceptors by selective 5-HT 1A receptor antagonists, or in mice with 5-HT 1A receptor deletion, has been shown through in vivo microdialysis studies to facilitate the effect of SSRIs on extracellular 5-HT levels in various terminal regions of rat brain (Hjorth, 1993;Hjorth and Auerbach, 1994;Knobelman et al, 2001b;Parsons et al, 2001). SSRIs given in combination with 5-HT 1B receptor antagonists or in 5-HT 1B receptor knockout mice also augment 5-HT outflow compared to SSRI treatment alone (Knobelman et al, 2001b;Maswood et al, 1999;Malagie et al, 2001Malagie et al, , 2002. Thus, both 5-HT autoreceptors, the somatodendritic 5-HT 1A autoreceptor and the terminal 5-HT 1B autoreceptor, can be involved in regulating the release of 5-HT during pharmacological or behavioral activation.…”

Section: Introductionmentioning

confidence: 99%

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Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

Jones

Lucki

2005

Neuropsychopharmacol

100

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Few studies have examined the relationship between genetics, stress, and sex-linked differences in neurotransmitter systems. Examining serotonin (5-HT) receptor knockout mice on stress-induced behavioral depression, female 5-HT 1B receptor knockout mice demonstrated significantly reduced immobility than either male 5-HT 1B receptor knockout mice or male and female wild-type mice on the tail suspension test (TST) and forced swimming test. The behavioral phenotype was identified as likely due to a disinhibition of 5-HT release, because depletion of 5-HT with parachlorophenylalanine selectively reduced immobility of female 5-HT 1B receptor knockout mice in the TST. In contrast, male and female 5-HT 1A receptor knockout mice demonstrated reduced immobility compared with control mice, but the depletion of 5-HT with PCPA did not reverse the antidepressant-like phenotype. Microdialysis studies confirmed significantly higher baseline levels of hippocampal 5-HT in female, but not male, 5-HT 1B receptor knockout mice. Both male and female 5-HT 1B receptor knockout mice demonstrated augmented dialysate responses to fluoxetine. Also, both male and female 5-HT 1B receptor knockout mice demonstrated reductions of immobility in the TST after treatment with fluoxetine. Therefore, female 5-HT 1B receptor knockout mice demonstrate a sex-linked disinhibition of 5-HT release that sustained higher baseline levels of hippocampal 5-HT and behavioral vulnerability to 5-HT depletion.

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Section: -Ht Microdialysis Measurementmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

Jones

Lucki

2005

Neuropsychopharmacol

100

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“…In some brain regions, serotonin fluctuates with changes in behavioral context like imposition of a stressor and changes in social group composition (De Souza and Van Loon, 1986;Kawahara et al, 1993;Adell et al, 1997;Price et al, 1998;Chaouloff et al, 1999;Hall et al, 2011;Hall et al, 2012). Brain serotonin is also sensitive to internal influences such as reproductive state and sex (Maswood et al, 1999;Jitsuki et al, 2009). Estrogen levels, which fluctuate across female reproductive state and differ between the sexes, influence serotonergic function in sensory brain regions (Rubinow et al, 1998;Abizaid et al, 2005;Matragrano et al, 2012).…”

Section: Research Articlementioning

confidence: 99%

Context-dependent fluctuation of serotonin in the auditory midbrain: the influence of sex, reproductive state, and experience

Hanson

Hurley

2013

Journal of Experimental Biology

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In the face of changing behavioral situations, plasticity of sensory systems can be a valuable mechanism to facilitate appropriate behavioral responses. In the auditory system, the neurotransmitter serotonin is an important messenger for context-dependent regulation because it is sensitive to both external events and internal state, and it modulates neural activity. In male mice, serotonin increases in the auditory midbrain region, the inferior colliculus (IC), in response to changes in behavioral context such as restriction stress and social contact. Female mice have not been measured in similar contexts, although the serotonergic system is sexually dimorphic in many ways. In the present study, we investigated the effects of sex, experience and estrous state on the fluctuation of serotonin in the IC across contexts, as well as potential relationships between behavior and serotonin. Contrary to our expectation, there were no sex differences in increases of serotonin in response to a restriction stimulus. Both sexes had larger increases in second exposures, suggesting experience plays a role in serotonergic release in the IC. In females, serotonin increased during both restriction and interactions with males; however, the increase was more rapid during restriction. There was no effect of female estrous phase on the serotonergic change for either context, but serotonin was related to behavioral activity in females interacting with males. These results show that changes in behavioral context induce increases in serotonin in the IC by a mechanism that appears to be uninfluenced by sex or estrous state, but may depend on experience and behavioral activity.

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“…111 It has been shown, for example, that 5-HT concentrations fluctuate throughout the rodent estrus cycle. 112,113 Estrogen has been reported to increase TPH production in non-human primates. 114 Furthermore, estrogen can alter the expression of genes involved in the 5-HTergic system and can enhance 5-HTergic activity.…”

Section: Gendermentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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Estrous cycle modulation of extracellular serotonin in mediobasal hypothalamus: role of the serotonin transporter and terminal autoreceptors

Cited by 103 publications

References 45 publications

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

Sex Differences in the Regulation of Serotonergic Transmission and Behavior in 5-HT Receptor Knockout Mice

Context-dependent fluctuation of serotonin in the auditory midbrain: the influence of sex, reproductive state, and experience

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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