Ovarian steroid effects on serotonin 1A, 2A and 2C receptor mRNA in macaque hypothalamus

Gundlah, Chrisana; Pecins‐Thompson, Melanie; Schutzer, William E.; Bethea, Cynthia L.

doi:10.1016/s0169-328x(98)00295-2

Cited by 99 publications

(79 citation statements)

References 60 publications

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“…The 5HT1A receptor is the major inhibitory serotonin receptor, but 5HT1A mRNA expression is not robust in the PVN of macaques and 5HT1A binding is decreased and/or desensitized by E treatment (Gundlah et al, 1999;Lu and Bethea, 2002;Carrasco et al, 2004). 5HT2A and 5HT2C receptors are prominent in the PVN, but they are stimulatory (Gundlah et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

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Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Bethea

Centeno

2007

Neuropsychopharmacol

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Corticotropin-releasing hormone (CRH) gene and protein expression were examined in the paraventricular nucleus (PVN) of ovariectomized female macaques treated with placebo or hormone therapy (HT) consisting of either estrogen (E) for 28 days, or progesterone (P) for the last 14 of 28 days, or E for 28 days supplemented with P for the last 14 of 28 days using Silastic capsules implanted s.c. in the periscapular region (n ¼ 4/group). Perfusion fixed sections (25 mm) at five levels of the PVN (rostral to caudal at 250 mm intervals) were immunostained (ICC) with an antibody to human CRH or processed in an in situ hybridization (ISH) assay with a monkey specific CRH riboprobe. The immunostained CRH-positive area was quantified with a Marianas Stereology Workstation and Slidebook 4.2. There was a significant decrease in the immunological CRH signal with E, P, and E + P treatment as measured by total or average pixels and microns (analysis of variance (ANOVA), po0.002; Student-Newman-Keul's post hoc test versus placebo control group, po0.05). There was also a decrease in the number of detectable CRH neurons (ANOVA, po0.03) with HT. The sections processed for ISH were exposed to autoradiographic films. The CRH mRNA signal was analyzed with NIH Image. The average optical density and positive pixel area of the CRH mRNA signal was significantly suppressed by ovarian HT (ANOVA po0.002; StudentNewman-Keul's post hoc test versus placebo control group, po0.05). In summary, 1 month of stable treatment with a moderate dose of E, P or E + P significantly reduced CRH mRNA and protein in the PVN of ovariectomized monkeys. These results suggest that this hormone treatment regimen may increase stress resilience in surgically menopausal primates.

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Section: Discussionmentioning

confidence: 99%

“…The protocol and buffers for the ISH assay have been published previously (Gundlah et al, 1999;Sanchez et al, 2005). A recombinant partial cDNA clone of the CRH gene was constructed using forward and reverse primers that produced a 202 bp segment corresponding to the region that codes for the CRH peptide from human (NM_000756).…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Bethea

Centeno

2007

Neuropsychopharmacol

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“…The neuroendocrine response to serotonergic activation has been used as a diagnostic tool to examine the functioning of serotonergic neurons in the brains of patients suffering from mood disorders (Lerer, et al, 1999). The presence of 5-HT 2A receptors in the hypothalamic PVN is supported by autoradiographic (Appel, et al, 1990), in situ hybridization (Gundlah, et al, 1999;Wright, et al, 1995) and immunohistochemical labeling studies (Zhang, et al, 2002). 5-HT 2A receptors in the hypothalamic PVN mediate the neuroendocrine responses to an acute peripheral injection of the selective 5-HT 2A/C receptor agonist, DOI.…”

Section: Introductionmentioning

confidence: 99%

Sustained treatment with a 5-HT2A receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT2A receptors despite increases in receptor protein levels in rats

Landry

Carrasco

et al. 2008

Neuropharmacology

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SummaryAdaptive changes in serotonin2A (5-HT 2A ) receptor signaling are associated with the clinical response to a number of psychiatric drugs including atypical antipsychotics and selective serotonin reuptake inhibitors. The present study examined possible mechanisms of agonist-induced desensitization of 5-HT 2A receptors in rat hypothalamic paraventricular nucleus (PVN) after 4 and 7 days of treatment with 1 mg/kg (-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The magnitude of 5-HT 2A receptor-mediated oxytocin release decreased 78% after 4 days and 61% after 7 days of DOI treatment. Similarly, the magnitude of ACTH release following 1 mg/kg DOI decreased by 31% after 4 days and 38% after 7 days of DOI treatment. Treatment with DOI for either 4 or 7 days caused a significant decrease (by approximately 50%) in the high affinity 5-HT 2A receptor binding as measured by 125 I-DOI binding compared to saline-treated control rats. In contrast, western blot analysis demonstrated a significant increase in 5-HT 2A receptor protein levels with 4 or 7 days of DOI treatment to 167% and 191% of control levels respectively. Real time quantitative RT-PCR analysis revealed a small but nonsignificant increase in the levels of 5-HT 2A mRNA following treatment with DOI for 4 or 7 days. Taken together, the 5-HT 2A receptor-stimulated hormone responses, agonist binding data and western blot data suggest that although agonist treatment increases the levels of 5-HT 2A receptor protein in the cell membrane, there is a reduction in the population of 5-HT 2A receptors capable of high-affinity binding and mediating a functional response.

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“…A Kv subunit is composed of a voltage-sensing region (S1 through S4), a pore region (S5-H5-S6) with the n-and C-termini residing inside the cell. A functional channel is formed by the assembling of four α-subunits hypothalamus, 5-Ht 2A R mRnA is more abundantly localized to paraventricular nucleus neurons that release CRH (Gundlah et al 1999); 5-Ht 2A Rs have been implicated in schizophrenia, depression, and psychotomimetic effects of hallucinogens, such as LSD. the mescaline analog DOI, which stimulates 5-Ht 2 R, enhances glutamate release onto layer V pyramidal neurons (Aghajanian and Marek 1997); 5-Ht 2A Rs stimulation by 5-Ht has also been implicated in hyperexcitation of frontal cortex, sensory perturbations, sleep difficulties, and psychosis (Vollenweider et al 1997;Hermle et al 1998;Oberndorfer et al 2000).…”

Section: -Ht 2 Receptorsmentioning

confidence: 99%

“…However, they are widely distributed in several areas of the cortex (olfactory nucleus, pyriform, cingulate, and retrosplenial), limbic system (nucleus accumbens, hippocampus, amygdala), basal ganglia (caudate nucleus, substantia nigra), and hypothalamus (arcuate region) (Di Giovanni et al 2006Giovanni et al , 2011Gundlah et al 1999). In the external globus pallidus, 5-Ht 2C Rs are likely located presynaptically, on the axon terminals of afferent neurons.…”

Section: -Ht 2 Receptorsmentioning

confidence: 99%

5-HT2 receptors-mediated modulation of voltage-gated K+ channels and neurophysiopathological correlates

et al. 2013

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The activity of voltage-gated K(+) channels (Kv) can be dynamically modulated by several events, including neurotransmitter stimulated biochemical cascades mediated by G protein-coupled receptors such as 5-HT2 receptors (5-HT2Rs). Activation of 5-HT2A/CR inhibits the Shaker-like K(+) channels Kv1.1 and Kv1.2, and this modulation involves the dual coordination of both RPTPα and distinct tyrosine kinases coupled to this receptor; 5-HT2Rs-mediated modulation of Kv channels controls glutamate release onto prefrontal cortex neurons that might play critical roles in neurophysiological, neurological, and psychiatric conditions. Noticeably, hallucinogens modulate Kv channel activity, acting at 5-HT2R. Hence, comprehensive knowledge of 5-HT2R signaling through modulation of distinct K(+) channels is a pivotal step in the direction that will enable scientists to discover novel 5-HT functions and dysfunctions in the brain and to identify original therapeutic targets.peer-reviewe

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Ovarian steroid effects on serotonin 1A, 2A and 2C receptor mRNA in macaque hypothalamus

Cited by 99 publications

References 60 publications

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Ovarian Steroid Treatment Decreases Corticotropin-Releasing Hormone (CRH) mRNA and Protein in the Hypothalamic Paraventricular Nucleus of Ovariectomized Monkeys

Sustained treatment with a 5-HT2A receptor agonist causes functional desensitization and reductions in agonist-labeled 5-HT2A receptors despite increases in receptor protein levels in rats

5-HT2 receptors-mediated modulation of voltage-gated K+ channels and neurophysiopathological correlates

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