Hippocampal 5-hydroxytryptamine synthesis is greater in female rats than in males and more decreased by the 5-HT1A agonist 8-OH-DPAT

Haleem, Darakhshan Jabeen; Kennett, Guy A.; Curzon, G.

doi:10.1007/bf01251004

Cited by 109 publications

(42 citation statements)

References 38 publications

(39 reference statements)

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“…5-HT 1A receptor binding potentials are higher, but 5-HT transporter (5-HTT) bindings are lower in cortical and subcortical regions in women than in men (14). Animal studies also suggest that dimorphisms are implicated in gender differences of cerebral 5-HT levels in the hippocampus and amygdala (15) and the hippocampal 5-HT synthesis (16) is greater in female rats than in the males. Behavioral studies have shown differential sensitivities to various kinds of stresses such as novel environment in the open field test (17,18), swim stress (19), and eye-blink conditioning (20) between the males and females.…”

Section: Metaplastic Regulation Of the Median Raphe Nucleus Via Serotmentioning

confidence: 85%

Metaplastic Regulation of the Median Raphe Nucleus via Serotonin 5-HT1A Receptor on Hippocampal Synaptic Plasticity Is Associated With Gender-Specific Emotional Expression in Rats

et al. 2014

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Abstract. Gender differences in psychiatric disorders are considered to be associated with the serotonergic (5-HTergic) system; however the underlying mechanisms have not been clearly elucidated. In this study, possible involvement of the median raphe nucleus (MRN)-hippocampus 5-HTergic system in gender-specific emotional regulation was investigated, focusing on synaptic plasticity in rats. A behavioral study using a contextual fear conditioning (CFC) paradigm showed that the females exhibited low anxiety-like behavior. Extracellular 5-HT levels in the hippocampus were increased by CFC only in the males. Long-term potentiation (LTP) in the hippocampal CA1 field was suppressed after CFC in the males, which was mimicked by the synaptic response to MRN electrical stimulation. In the MRN, 5-HT immunoreactive cells significantly increased in the females compared with those in the males. Pretreatment with the 5-HT 1A receptor agonists tandospirone (10 mg/kg, i.p.) and 8-OH DPAT (3 mg/kg, i.p.) significantly suppressed LTP induction in the males. Synaptic responses to CFC and 5-HT 1A receptor interventions were not observed in the females. These results suggest that the metaplastic 5-HTergic mechanism via 5-HT 1A receptors in the MRN-hippocampus pathway is a key component for gender-specific emotional regulation and may be a cause of psychiatric disorders associated with vulnerability or resistance to emotional stress.

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Section: Metaplastic Regulation Of the Median Raphe Nucleus Via Serotmentioning

confidence: 85%

Metaplastic Regulation of the Median Raphe Nucleus via Serotonin 5-HT1A Receptor on Hippocampal Synaptic Plasticity Is Associated With Gender-Specific Emotional Expression in Rats

et al. 2014

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“…Reports of sex differences related to the 5-HTergic system come from animal and human studies. Female rats exhibit increased 5-HT activity in the dorsal raphe nuclei, 101 higher 5-HT levels in the brain stem and limbic forebrain, 102 higher 5-HT synthesis 103 and turnover. 104 The average firing activity of 5-HT neurons has also been found to be higher in males than in cycling females.…”

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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“…The synthesis and release of 5-HT in all brain regions including the hippocampus [20][21][22]99] is under the control of an effective feedback mechanism involving the stimulation of 5-HT-1A receptors located on the soma and dendrites [100] of the serotonergic neurons in the raphe nucleus. 5-HT1B receptors located at the terminal ends of the serotonergic neurons [101] also control the release of 5-HT via a feedback mechanism [102].…”

Section: Raphe-hippocampal Serotonin Neuro-transmission and Adaptatiomentioning

confidence: 99%

“…The 5-HT-1A receptor is a G-protein-coupled receptor widely distributed in regions that receive serotonergic input from the raphe nuclei: the frontal cortex, septum, amygdale, hippocampus and hypothalamus [18,19]. It also serves as somatodendritic autoreceptor of raphe nuclei reducing the firing rate of serotonergic neurons [8,[20][21][22]. The hippocampus has been extensively studied with regard to stress, depression and antidepressant action [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Raphe-Hippocampal Serotonin Neurotransmission In The Sex Related Differences of Adaptation to Stress: Focus on Serotonin-1A Receptor

Haleem¹

2011

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Stress is the major predisposing and precipitating factor in the onset of depression which is the most significant mental health risk for women. Behavioral studies in animal models show that female sex though less affected by an acute stressor; exposure to repeated stressors induces coping deficits to impair adaptation in them. A decrease in the function of 5-hydroxytryptamine (5-HT; serotonin) in the hippocampus and an increased function of the 5-HT-1A receptor in the raphe nucleus coexist in depression. Pharmacological and neurochemical data are relevant that facilitation of serotonin neurotransmission via hippocampus due to desensitization of somatodendritic 5-HT1A receptors may lead to adaptation to stress. The present article reviews research on sex related differences of raphe-hippocampal serotonin neurotransmission to find a possible answer that may account for the sex differences of adaptation to stress reported in preclinical research and greater incidence of depression in women than men.

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Hippocampal 5-hydroxytryptamine synthesis is greater in female rats than in males and more decreased by the 5-HT1A agonist 8-OH-DPAT

Cited by 109 publications

References 38 publications

Metaplastic Regulation of the Median Raphe Nucleus via Serotonin 5-HT1A Receptor on Hippocampal Synaptic Plasticity Is Associated With Gender-Specific Emotional Expression in Rats

Metaplastic Regulation of the Median Raphe Nucleus via Serotonin 5-HT1A Receptor on Hippocampal Synaptic Plasticity Is Associated With Gender-Specific Emotional Expression in Rats

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Raphe-Hippocampal Serotonin Neurotransmission In The Sex Related Differences of Adaptation to Stress: Focus on Serotonin-1A Receptor

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