Corticosteroids regulate 5-HT1A but not 5-HT1B receptor mRNA in rat hippocampus

Neumaier, John F.; Sexton, Timothy J.; Hamblin, Mark W.; Beck, Sheryl G.

doi:10.1016/s0169-328x(00)00181-9

Cited by 48 publications

(27 citation statements)

References 42 publications

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“…To our knowledge, the effects of glucocorticoids on the function of 5-HT 1B terminal autoreceptors (as opposed to postsynaptic 5-HT 1B receptors) has not been reported. Although corticosteroids have been shown to be without influence on 5-HT 1B receptor mRNA expression in the DRN (Neumaier et al, 2000), changes in 5-HT 1B receptor function downstream of transcription are possible.…”

Section: Flattened Glucocorticoid Rhythmmentioning

confidence: 98%

Altered Glucocorticoid Rhythm Attenuates the Ability of a Chronic SSRI to Elevate Forebrain 5-HT: Implications for the Treatment of Depression

Gartside

Leitch

Young

2003

Neuropsychopharmacol

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Both glucocorticoids and selective serotonin reuptake inhibitors (SSRIs) alter aspects of 5-HT function including somatodendritic 5-HT 1A autoreceptor sensitivity. Many depressed patients prescribed SSRIs have pre-existing flattened diurnal gluococorticoid rhythm. In these patients, interactions between flattened glucocorticoid rhythm and chronic SSRIs, which impact on the SSRI's ability to elevate forebrain 5-HT, may alter clinical efficacy. To address this issue rats underwent implantation of slow-release corticosterone (75 mg pellet s.c.) (to flatten the glucocorticoid rhythm) or sham surgery, and injection of fluoxetine (10 mg/kg/day i.p., 12 days) or vehicle. Using microdialysis in the frontal cortex we found that (21 h after the last injection) extracellular 5-HT was elevated in fluoxetine-or corticosterone-treated animals, but not in those treated with corticosterone plus fluoxetine. In fluoxetine-treated animals, blockade of terminal reuptake by local perfusion of fluoxetine increased 5-HT to the same level as it did in controls, suggesting normal terminal 5-HT release after chronic fluoxetine. However, 5-HT levels following local reuptake blockade in both the corticosterone and corticosterone plus fluoxetine groups were lower than controls, suggesting a corticosterone-induced decrease in terminal release. Finally in fluoxetine, corticosterone, and corticosterone plus fluoxetine groups, there was marked 5-HT 1A receptor desensitization, evidenced by attenuation of the decrease in 5-HT release following systemic fluoxetine injection. The data indicate that, despite desensitization of 5-HT 1A autoreceptors, concurrent flattened glucocorticoid rhythm compromises the ability of SSRIs to elevate forebrain 5-HT. These findings suggest a potential mechanism for the reduced antidepressant efficacy of SSRIs in those patients with pre-existing glucocorticoid abnormalities.

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Section: Flattened Glucocorticoid Rhythmmentioning

confidence: 98%

Altered Glucocorticoid Rhythm Attenuates the Ability of a Chronic SSRI to Elevate Forebrain 5-HT: Implications for the Treatment of Depression

Gartside

Leitch

Young

2003

Neuropsychopharmacol

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“…For the 5-HT 1B studies, three oligonucleotides corresponding to base pairs 1343-1382, 1630-1668, and 1790-1829 of the rat 5-HT 1B clone, MG11B (Hamblin et al, 1992) were used. For 5-HT 1A probes, one oligonucleotide corresponding to base pairs 1110-1151 was used (Neumaier et al, 2000). For SERT probes, two oligonucleotides corresponding to base pairs 101 to 149 and 570 to 618 of the rat serotonin transporter sequence were used (Blakely et al, 1991).…”

Section: In Situ Hybridization Histochemistrymentioning

confidence: 99%

“…The slides were rinsed in distilled water, dehydrated through a series of graded alcohol rinses containing 300 mM ammonium acetate, and air dried. Autoradiographic signal was detected using a Cyclone storage phosphor scanner (Packard Instruments, Meridian, CT) at 600 dpi resolution and were stored on CD-ROM disks; exposure times were 24-26 h (Neumaier et al, 2000, Clark et al, 2006. Tph2 in situ hybridization histochemistry was performed essentially as previously described (Clark et al, 2006).…”

Section: In Situ Hybridization Histochemistrymentioning

confidence: 99%

“…In brief, tissue sections were thawed at room temperature and fixed in cold 4% paraformaldehyde. After rinsing in phosphate-buffered saline, sections were treated with acetic anhydride (0.25% in 0.1 M triethanolamine), dehydrated, delipidated, and air-dried.In situ hybridization histochemistry for 5-HT 1A , 5-HT 1B , and SERT was performed using synthetic oligonucleotides as described previously (Neumaier et al, 1996, Neumaier et al, 1997, Neumaier et al, 2000, Clark et al, 2006. For the 5-HT 1B studies, three oligonucleotides corresponding to base pairs 1343-1382, 1630-1668, and 1790-1829 of the rat 5-HT 1B clone, MG11B (Hamblin et al, 1992) were used.…”

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confidence: 99%

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Chronic low dose ovine corticotropin releasing factor or urocortin II into the rostral dorsal raphe alters exploratory behavior and serotonergic gene expression in specific subregions of the dorsal raphe

et al. 2007

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Corticotropin releasing factor (CRF) family peptides play key roles in integrating neural responses to stress. Both major CRF receptors have been pharmacologically identified in the dorsal raphe nucleus (DRN), a stress sensitive and internally heterogeneous nucleus supplying many forebrain regions with serotonergic input. Despite the involvement of chronic stress and serotonergic dysfunction in human mood and anxiety disorders, little is known about the effects of chronic CRF receptor activation on the DRN. We infused ovine CRF (1ng/hr), urocortin II (UCNII, 1ng/hr), or vehicle alone into rat DRN over 6 days. During infusion, animals were allowed to freely explore an open field for 15 minutes on each of two days, with the addition of a novel object on the second day. Following behavioral testing, 5-HT 1A , 5-HT 1B , serotonin transporter (SERT), and tryptophan hydroxylase-2 (Tph2) expression were examined through the DRN by in situ hybridization. Ovine CRF infusion resulted in significantly decreased novel object touches, climbs, as well as increased latency to first novel object contact. UCNII had a similar but less dramatic effect, decreasing only climbing behavior. Both ovine CRF and UCNII blunted the decrease in corner time expected on reexposure to the open field. Both peptides also produced regionally specific changes in gene expression: 5-HT 1A expression was increased 30% in the mid-rostral ventromedial DRN, while SERT was decreased by 30% in the mid-caudal shell dorsomedial DRN. There also appeared to be a shift in the relative level of Tph2 expression between the ventromedial and core dorsomedial DRN at the mid-rostral level. Changes in 5-HT 1A , SERT, and relative Tph2 mRNA abundance were correlated with novel object exploration. These findings suggest chronic intra-DRN administration of CRF agonists decreases exploratory behavior, while producing subregionally limited changes in serotonergic gene expression. These studies may be relevant to mechanisms underlying behavioral changes after chronic stress. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptDepression and anxiety disorders are among the leading causes of morbidity, mortality, and disability in the United States (Greenberg et al., 2003). They are often comorbid, and both are highly associated with chronic exposure to stress. Multiple lines of evidence suggest that chronic and inescapable stress produce long lasting effects on brain function and behavior that play a prominent role in the development, maintenance, and recurrence of both depression and a variety of anxiety disorders (Gulley and Nemeroff, 1993, Arborelius et al., 1999, Ressler and Nemeroff, 2000.Altered serotonin neurotransmission appears to be a central mechanism inducing both depressive (Maes and Meltzer, 1995) and anxiety disorders (Ressler and Nemeroff, 2000). The majority of serotonergic fibers to forebrain regions thought to be involved in mood and anxiety regulation arise from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) ...

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“…Moreover, serotonin is involved in the regulation of the HPA axis [100]. The downregulation of 5-HT1A receptors in the hippocampus by stressors is corticoiddependent and reversed by antidepressants [101,102]. Indeed, patients with depression have reduced 5-HT1A receptor binding as revealed by positron emission tomography (PET) studies [103,104] plus results of altered receptor number in post-mortem investigations [105,106].…”

Section: Neurotransmitter Hypothesesmentioning

confidence: 99%