Chronic Fluoxetine Reduces Serotonin Transporter mRNA and 5-HT1B mRNA in a Sequential Manner in the Rat Dorsal Raphe Nucleus

Neumaier, John F.; Root, Daniel C; Hamblin, Mark W.

doi:10.1016/s0893-133x(96)00095-4

Cited by 126 publications

(82 citation statements)

References 39 publications

(52 reference statements)

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“…1). The anatomical distribution of each mRNA species conformed to previously published descriptions [8,30]. As previously reported [31], 5-HT 1B mRNA density was too low in median raphe to quantify reliably (Fig.…”

Section: Resultssupporting

confidence: 88%

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

Neumaier

Sexton

Hamblin

et al. 2000

Molecular Brain Research

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The role of mineralocorticoid and glucocorticoid receptors (MR and GR, respectively) in the regulation of serotonin receptors has not been clearly delineated. There is no consensus regarding the regulation of 5-HT 1A receptors, and corticosteroid regulation of 5-HT 1B mRNA has not been previously studied. We compared the effects of long-term (two week) adrenalectomy (no MR or GR activation) and several hormone replacement protocols designed to stimulate MR selectively (ALDO), MR and GR (HCT), and continuous MR with cyclical GR activation (SHAM adrenalectomy). 5-HT 1A and 5-HT 1B mRNAs were measured by in situ hybridization in hippocampus and raphe nuclei. None of the experimental manipulations altered 5-HT 1B mRNA levels in the hippocampus or dorsal raphe, and also had no effect on 5-HT 1A mRNA in dorsal or median raphe. However, 5-HT 1A mRNA levels were regulated in a complex manner in the different subfields of hippocampus. We conclude that both MR and GR play an integrated role in regulating 5-HT 1A mRNA levels in hippocampus while having no effect on 5-HT 1B mRNA levels under these conditions.

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Section: Resultssupporting

confidence: 88%

“…Both 5-HT 1A and 5-HT 1B receptors serve as autoreceptors in serotonergic cells and heteroreceptors in other neurons. 5-HT 1B autoreceptors are selectively regulated by fluoxetine [1,30] and chemical axotomy with 5,7-dihydroxytryptamine [31]. 5-HT 1A receptors are also regulated in a cell specific manner.…”

Section: Discussionmentioning

confidence: 99%

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

Neumaier

Sexton

Hamblin

et al. 2000

Molecular Brain Research

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“…In this group of suicide victims, ethanol was detected in five suicide subjects and antidepressant drugs (clomipramine, fluoxetine, and mianserin) were detected in four depressed suicides. However, neither the above drugs nor electrocution or carbon monoxide influenced the transcription rate of adrenoceptors, serotonin receptors, or m-opioid receptors, except alcohol and fluoxetine that induced reductions in 5-HT 1B mRNA (Neumaier et al, 1996;Vazquez et al, 2002). In six suicides no toxicological screening data were available.…”

Section: Subject Selection and Brains Samplesmentioning

confidence: 97%

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

Escribá

Ozaita

Garcı́a-Sevilla

2004

Neuropsychopharmacol

121

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The development of new therapies for the treatment of psychiatric disorders requires an in-depth knowledge of the molecular bases underlying these pathologies, which remain largely unknown. Alterations in adrenoceptors, serotonin receptors, and other G proteincoupled receptors (GPCRs) have been associated with suicide and depression. However, to date, there is little information about mRNA expression of the GPCRs in the frontal cortex of suicide victims. Our goal was to study the expression in the brain of these receptors. For this purpose, we measured mRNA levels by RT-PCR. We found that the expressions of a 2A -adrenoceptors, 5-HT 1A , 5-HT 2A serotonin receptors, and m-opioid receptors were elevated in the post-mortem brains of these suicide victims with respect to matched controls. Moreover, in the case of a 2A -adrenoceptors (the only for which these data were available), a significant correlation was observed between the level of mRNA and protein quantified in the brain of the same subjects, indicating that protein synthesis of this receptor was not influenced by post-translational regulatory mechanisms. In addition, the degree of adrenoceptor and 5-HT receptor expressions appeared to be correlated in the brains of suicide victims and control subjects. Alterations in the expression of adrenoceptors, serotonin, and opioid receptors indicate that these signaling proteins might be related to the etiopathology of suicidal and depressive behaviors. Alternatively, such changes may represent adaptive mechanisms to compensate for other as yet unknown alterations. The results also suggest that these receptors could share common regulatory mechanisms.

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“…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.…”

mentioning

confidence: 99%

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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Chronic Fluoxetine Reduces Serotonin Transporter mRNA and 5-HT1B mRNA in a Sequential Manner in the Rat Dorsal Raphe Nucleus

Cited by 126 publications

References 39 publications

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

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

Increased mRNA Expression of α2A-Adrenoceptors, Serotonin Receptors and μ-Opioid Receptors in the Brains of Suicide Victims

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

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