Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain

Vicentic, Aleksandra; Francis, Darlene D.; Moffett, Mark C.; Lakatos, Anita; Rogge, George A.; Hubert, George W.; Harley, Jill; Kuhar, Michael J.

doi:10.1016/j.neuroscience.2006.02.008

Cited by 87 publications

(61 citation statements)

References 79 publications

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“…In rats, maternal separation decreases 5-HT functioning in amygdala, including reduced 5-HT levels, 5-HT1A autoreceptors, and 5-HT transporters (Vicentic et al, 2006;Oreland et al, 2009). In monkeys, peer-reared adults have decreased 5-HT transporters measured by PET in amygdala and related structures compared with maternal-reared adults (Ichise et al, 2006).…”

Section: B Social Influencesmentioning

confidence: 99%

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

2013

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Section: B Social Influencesmentioning

confidence: 99%

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

2013

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“…Similarly, bipolar depressed patients were more likely to be hospitalized after recent stress if they had the G/G Htr1a genotype [176]. In animal models, early life stress leads to region-specific alterations in 5-HT 1A receptor levels [177,178] and appears to interact with late life stress to induce deficits in 5-HT 1A receptor signalling [179]. Thus, stress-induced dysregulation of 5-HT 1A receptor expression may be exacerbated by the presence of the G-allele, leading to increased predisposition to mental illness.…”

Section: Association Studies Of Htr1a Polymorphisms In Depression-andmentioning

confidence: 99%

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Albert

2012

Phil. Trans. R. Soc. B

115

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The serotonin-1A (5-HT 1A ) receptor is an abundant post-synaptic 5-HT receptor (heteroreceptor) implicated in regulation of mood, emotion and stress responses and is the major somatodendritic autoreceptor that negatively regulates 5-HT neuronal activity. Based on animal models, an integrated model for opposing roles of pre-and post-synaptic 5-HT 1A receptors in anxiety and depression phenotypes and response to antidepressants is proposed. Understanding differential transcriptional regulation of pre-versus post-synaptic 5-HT 1A receptors could provide better tools for their selective regulation. This review examines the transcription factors that regulate brain region-specific basal and stress-induced expression of the 5-HT 1A receptor gene (Htr1a). A functional polymorphism, rs6295 in the Htr1a promoter region, blocks the function of specific repressors Hes1, Hes5 and Deaf1, resulting in increased 5-HT 1A autoreceptor expression in animal models and humans. Its association with altered 5-HT 1A expression, depression, anxiety and antidepressant response are related to genotype frequency in different populations, sample homogeneity, disease outcome measures and severity. Preliminary evidence from gene Â environment studies suggests the potential for synergistic interaction of stress-mediated repression of 5-HT 1A heteroreceptors, and rs6295-induced upregulation of 5-HT 1A autoreceptors. Targeted therapeutics to inhibit 5-HT 1A autoreceptor expression and induce 5-HT 1A heteroreceptor expression may ameliorate treatment of anxiety and major depression.

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“…The level of 5-HT1A-R binding in basolateral nucleus of the amygdala (BLA) is increased by maternal separation stress in rats (Vicentic et al, 2006) and Octodon degus (Ziabreva et al, 2003). Under non-stressed conditions, application of 5-HT1A-R agonists (e.g., 8-OH-DPAT) inhibits the excitability of neurons in the BLA, while the inhibitory actions of 5-HT on these neurons can be prevented by 5-HT1A-R antagonist coapplication (Cheng et al, 1998;Stein et al, 2000;Wang et al, 1999).…”

Section: Role Of 5-ht1a Receptorsmentioning

confidence: 99%

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

Holmes

2008

Neuroscience & Biobehavioral Reviews

243

166

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The serotonin system is strongly implicated in the pathophysiology and therapeutic alleviation of stress-related disorders such as anxiety and depression. Serotonergic modulation of the acute response to stress and the adaptation to chronic stress is mediated by a myriad of molecules controlling serotonin neuron development (Pet-1), synthesis (tryptophan hydroxylase 1 and 2 isozymes), packaging (vesicular monoamine transporter 2), actions at presynaptic and postsynaptic receptors (5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT3A, 5-HT4, 5-HT5A, 5-HT6, 5-HT7), reuptake (serotonin transporter), and degradation (monoamine oxidase A). A growing body of evidence from preclinical rodents models, and especially genetically modified mice and inbred mouse strains, has provided significant insight into how genetic variation in these molecules can affect the development and function of a key neural circuit between the dorsal raphe nucleus, medial prefrontal cortex and amygdala. By extension, such variation is hypothesized to have a major influence on individual differences in the stress response and risk for stress-related disease in humans. The current article provides an update on this rapidly evolving field of research.

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Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain

Cited by 87 publications

References 79 publications

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

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Maternal separation alters serotonergic transporter densities and serotonergic 1A receptors in rat brain

Cited by 87 publications

References 79 publications

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Transcriptional regulation of the 5-HT1Areceptor: implications for mental illness

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

Contact Info

Product

Resources

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Transcriptional regulation of the 5-HT_1Areceptor: implications for mental illness