Effects of chronic citalopram treatment on 5-HT1A and 5-HT2A receptors in group- and isolation-housed mice

Günther, Lydia; Liebscher, Sabine; Jähkel, M; Oehler, Jochen

doi:10.1016/j.ejphar.2008.07.011

Cited by 42 publications

(30 citation statements)

References 70 publications

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“…Because antipsychotics inhibit the 5-HT 2A receptor, the findings that 5-HT 2A receptor activation enhances contextual and cued fear (e) fit with the fact that psychoses can be associated with excessive fear sensations [133] and support the validity of the contextual/cued fear paradigm. Also the fact that chronic SSRI exposure downregulates 5-HT 1A and 5-HT 2A receptors [128, 134] fits with the findings that 5-HT 1A receptor activation (d) and 5-HT 2A inactivation decrease conditioned fear (e).…”

Section: Discussionsupporting

confidence: 57%

Serotonergic Modulation of Conditioned Fear

Homberg

2012

Scientifica

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Conditioned fear plays a key role in anxiety disorders as well as depression and other neuropsychiatric conditions. Understanding how neuromodulators drive the associated learning and memory processes, including memory consolidation, retrieval/expression, and extinction (recall), is essential in the understanding of (individual differences in vulnerability to) these disorders and their treatment. The human and rodent studies I review here together reveal, amongst others, that acute selective serotonin reuptake inhibitor (SSRI) treatment facilitates fear conditioning, reduces contextual fear, and increases cued fear, chronic SSRI treatment reduces both contextual and cued fear, 5-HT1A receptors inhibit the acquisition and expression of contextual fear, 5-HT2A receptors facilitates the consolidation of cued and contextual fear, inactivation of 5-HT2C receptors facilitate the retrieval of cued fear memory, the 5-HT3 receptor mediates contextual fear, genetically induced increases in serotonin levels are associated with increased fear conditioning, impaired cued fear extinction, or impaired extinction recall, and that genetically induced 5-HT depletion increases fear conditioning and contextual fear. Several explanations are presented to reconcile seemingly paradoxical relationships between serotonin levels and conditioned fear.

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Section: Discussionsupporting

confidence: 57%

Serotonergic Modulation of Conditioned Fear

Homberg

2012

Scientifica

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“…Further studies are needed to clarify whether ERα or any of its splice variants play a role in this mechanism. Because the effects of SSRIs occur slowly and are thought to involve desensitization of pre-synaptic and post-synaptic 5-HT 1A receptors (Bosker et al, 2001; Chaput et al, 1986; Czachura and Rasmussen, 2000; Rush et al, 2004; Li et al, 1997; Gunther et al, 2008; Raap et al, 1999, Bleir and de Montigny, 1994), elucidating the estrogen-receptor-mediated mechanisms that result in rapid desensitization of 5-HT 1A signaling will be important in the design of novel treatments that activate specific estrogen receptors in conjunction with SSRI therapy, for the improved treatment of depression and other mood disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Desensitization (attenuation) of both somatodendritic 5-HT 1A autoreceptor signaling in the midbrain dorsal raphe nucleus (DRN) and postsynaptic 5-HT 1A receptor signaling in the paraventricular nucleus (PVN) region of the hypothalamus are thought to contribute to the therapeutic efficacy of SSRIs (Lesch et al 1991, Sargent et al 1997, Bosker et al, 2001; Chaput et al, 1986; Czachura and Rasmussen, 2000; Lerer et al, 1999; Li et al, 1997; Gunther et al, 2008; Raap et al, 1999; Bleir and de Montigny, 1994), which can take three to 12 weeks to achieve (Rush et al, 2004). Multiple studies have provided direct evidence of a hyperactive hypothalamic-adreno-pituitary (HPA) axis response to the 5-HT 1A partial agonist buspirone, as evidenced by elevated adrenocorticotropic hormone (ACTH) and cortisol levels, which can be prevented by SSRI treatment (Navines et al, 2007; Gomez-Gil et al, 2010; Nikisch et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus

McAllister

Creech

Kimball

et al. 2012

Psychoneuroendocrinology

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Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT1A) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT1A receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT1A receptor desensitization. We previously showed that estrogen receptor β is not necessary for 5-HT1A receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT1A receptor as measured by hormonal responses to the selective 5-HT1A receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT1A receptor signaling components including 5-HT1A receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT1A receptor protein but increased 5-HT1A mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT1A receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT1A receptor signaling pathway and desensitization of 5-HT1A receptor signaling.

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“…Such relations may be established in early brain development (Gaspar et al, 2003). Chronic disturbances in serotonin homeostasis may affect 5-HT 2A receptor levels; increased synaptic serotonin is suggested to lead to 5-HT 2A receptor down-regulation (Meyer et al, 2001;Gunther et al, 2008), whereas low synaptic serotonin may up-regulate 5-HT 2A receptor levels (Cahir et al, 2007;Heal et al, 1985). The latter could be linked to high risk of developing mood disorders.…”

Section: Discussionmentioning

confidence: 99%

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

Frøkjær¹,

Vinberg

Erritzoe³

et al. 2009

Neuropsychopharmacol

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Life stress is a robust risk factor for later development of mood disorders, particularly for individuals at familial risk. Likewise, scoring high on the personality trait neuroticism is associated with an increased risk for mood disorders. Neuroticism partly reflects stress vulnerability and is positively correlated to frontolimbic serotonin 2A (5-HT 2A ) receptor binding. Here, we investigate whether neuroticism interacts with familial risk in relation to frontolimbic 5-HT 2A receptor binding. Twenty-one healthy twins with a co-twin history of mood disorder and 16 healthy twins without a co-twin history of mood disorder were included. They answered self-report personality questionnaires and underwent [ 18 F]altanserin positron emission tomography. We found a significant interaction between neuroticism and familial risk in predicting the frontolimbic 5-HT 2A receptor binding (p ¼ 0.026) in an analysis adjusting for age and body mass index. Within the high-risk group only, neuroticism and frontolimbic 5-HT 2A receptor binding was positively associated (p ¼ 0.0037). In conclusion, our data indicate that familial risk and neuroticism interact in their relation to frontolimbic 5-HT 2A receptor binding. These findings point at a plausible neurobiological link between genetic and personality risk factors and vulnerability to developing mood disorders. It contributes to our understanding of why some people at high risk develop mood disorders while others do not. We speculate that an increased stress reactivity in individuals at high familial risk for mood disorders might enhance the effect of neuroticism in shaping the impact of potential environmental stress and thereby influence serotonergic neurotransmission.

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Effects of chronic citalopram treatment on 5-HT1A and 5-HT2A receptors in group- and isolation-housed mice

Cited by 42 publications

References 70 publications

Serotonergic Modulation of Conditioned Fear

Serotonergic Modulation of Conditioned Fear

GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus

Familial Risk for Mood Disorder and the Personality Risk Factor, Neuroticism, Interact in Their Association with Frontolimbic Serotonin 2A Receptor Binding

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