Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat

Kim, Myung‐A; Lee, Hyun Sook; Lee, Beob Y.; Waterhouse, Barry D.

doi:10.1016/j.brainres.2004.08.022

Cited by 116 publications

(95 citation statements)

References 55 publications

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“…In fact, the 5-HT neurons receive a fairly dense noradrenergic innervation that exerts a tonic excitation via α 1 -adrenoreceptors (160). However, the contribution of this innervation from LC seems to be minor (143,(161)(162)(163)(164), and more caudally located catecholamine groups may be more important (164). Our results, based on double/triple labeling, are in agreement with this view, showing that the vast majority of galanin nerve terminals lack DBH at the levels analyzed in any case.…”

Section: Discussionsupporting

confidence: 87%

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Wang

Barde

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The neuropeptide galanin coexists in rat brain with serotonin in the dorsal raphe nucleus and with noradrenaline in the locus coeruleus (LC), and it has been suggested to be involved in depression. We studied rats exposed to chronic mild stress (CMS), a rodent model of depression. As expected, these rats showed several endophenotypes relevant to depression-like behavior compared with controls. All these endophenotypes were normalized after administration of a selective serotonin reuptake inhibitor. The transcripts for galanin and two of its receptors, galanin receptor 1 (GALR1) and GALR2, were analyzed with quantitative real-time PCR using laser capture microdissection in the following brain regions: the hippocampal formation, LC, and ventral periaqueductal gray (vPAG). Only Galr1 mRNA levels were significantly increased, and only in the latter region. After knocking down Galr1 in the vPAG with an siRNA technique, all parameters of the depressive behavioral phenotype were similar to controls. Thus, the depression-like behavior in rats exposed to CMS is likely related to an elevated expression of Galr1 in the vPAG, suggesting that a GALR1 antagonist could have antidepressant effects.dorsal raphe | neuropeptide | siRNA | stress | transmitter coexistence T he indoleamine hypothesis of depression was formulated some five decades ago (1, 2), in parallel with the catecholamine hypothesis (3, 4), and has been supported by the success of selective serotonin reuptake inhibitors (SSRIs) for treatment of major depression (MD) (5). However, in a considerable number of cases, SSRIs are associated with side effects or lack of efficacy. For example, after treatment with SSRIs, only one-third of patients obtain full remission of symptoms (6). Therefore, there is an ongoing search for new medications targeting mood disorders, such as MD and anxiety. Here, neuropeptides and their receptors, the most diverse family of neurotransmitters in the brain (7), have been extensively explored (5,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), including galanin and its three receptors.Galanin is a 29-aa (30-aa in humans) neuropeptide (18) with a wide distribution in the rat brain (19,20), where it is coexpressed with noradrenaline/norepinephrine (NA) in locus coeruleus (LC) neurons and with 5-hydroxytryptamine (5-HT) in dorsal raphe nucleus (DR) neurons (21-25). There are three galanin receptors, GALR1-GALR3, which all belong to the family of seven transmembrane-spanning, G protein-coupled receptors (26-29). They are found in many areas of the rat brain, as first shown with autoradiographic ligand-binding methodology (30, 31), and later with in situ hybridization (ISH)/quantitative real-time PCR (qPCR) (32-36). The galanin system has been associated with numerous physiological and pathophysiological functions (29), including depression-and anxiety-like behaviors.There is early evidence from studies on the rat that central administration of galanin influences mood-related behavior in a region-specific way (37, 38), and also that galanin is prodepres...

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Section: Discussionsupporting

confidence: 87%

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Wang

Barde

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition to CRF, Ucn-2, which is highly expressed in the locus ceruleus nucleus, may innervate the DRN via a known reciprocal connection between these two brain regions (Kim et al, 2004). Moreover, intra-DRN administration of Ucn-2 dose dependently increased 5-HT efflux in the basolateral amygdala (Amat et al, 2004) and caused behavioral changes associated with inescapable tail shock, which were effective at doses 100-fold lower than those required for CRF (Hammack et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Urocortin 2-Deficient Mice Exhibit Gender-Specific Alterations in Circadian Hypothalamus–Pituitary–Adrenal Axis and Depressive-Like Behavior

Chen¹,

Zorrilla²,

Smith³

et al. 2006

J. Neurosci.

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Gender differences in hypothalamus-pituitary-adrenal (HPA) axis activation and the prevalence of mood disorders are well documented. Urocortin 2, a recently identified member of the corticotropin-releasing factor family, is expressed in discrete neuroendocrine and stress-related nuclei of the rodent CNS. To determine the physiological role of urocortin 2, mice null for urocortin 2 were generated and HPA axis activity, ingestive, and stress-related behaviors and alterations in expression levels of CRF-related ligands and receptors were examined. Here we report that female, but not male, mice lacking urocortin 2 exhibit a significant increase in the basal daily rhythms of ACTH and corticosterone and a significant decrease in fluid intake and depressive-like behavior. The differential phenotype of urocortin 2 deficiency in female and male mice may imply a role for urocortin 2 in these gender differences.

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“…Experiments combining retrograde tracing with serotonin (5-HT) immunostaining have established that many nonserotonergic DRN neurons project extrinsically (Beitz et al, 1986;Ma et al, 1991;Petrov et al, 1992Petrov et al, , 1994 Van Bockstaele et al, 1993;Kirifides et al, 2001;Kim et al, 2004;Halberstadt and Balaban, 2006a). Nonserotonergic DRN projections are neurochemically heterogeneous, and may contain a number of transmitter substances, including glutamate (Schwarz and Schwarz, 1992;Kiss et al, 2002), dopamine (Pohle et al, 1984;Descarries et al, 1986;Yoshida et al, 1989;Stratford and Wirtshafter, 1990;Hasue and Shammah-Lagnado, 2002), GABA (Nanopoulos et al, 1982;Stamp and Semba, 1995;Ford et al, 1995;Jankowski and Sesack, 2002), nitric oxide (Xu and Hokfelt, 1997;Simpson et al, 2003), and neuropeptides such as vasoactive intestinal polypeptide (VIP) (Petit et al, 1995;Kozicz et al, 1998) and cholecystokinin Seroogy and Fallon, 1989).…”

Section: Nih Public Accessmentioning

confidence: 99%

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

Halberstadt

Balaban

2008

Journal of Chemical Neuroanatomy

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The dorsal raphe nucleus (DRN) contains both serotonergic and non-serotonergic projection neurons. Retrograde tracing studies have demonstrated that components of the basal forebrain and extended amygdala are targeted heavily by input from nonserotonergic DRN neurons. The object of this investigation was to examine the terminal distribution of nonserotonergic DRN projections in the basal forebrain and extended amygdala, using a technique that allows selective anterograde tracing of nonserotonergic DRN projections. To trace nonserotonergic DRN projections, animals were pretreated with nomifensine, desipramine and the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), 7 days prior to placing an iontophoretic injection of biotinylated dextran amine (BDA) into the DRN. In animals treated with 5,7-DHT, numerous nonserotonergic BDA-labeled fibers ascended to the basal forebrain in the medial forebrain bundle system. Some of these labeled fibers crossed through the lateral hypothalamus, bed nucleus of the stria terminalis, and substantial innominata. These fibers entered the amygdala through the ansa peduncularis and ramified within the central and basolateral amygdaloid nuclei. Other fibers entered the diagonal band of Broca and formed a dense plexus of labeled fibers in the dorsal half of the intermediate portion of the lateral septal nucleus and the septohippocampal nucleus. These findings demonstrate that the basal forebrain and extended amygdala receive a dense projection from nonserotonergic DRN neurons. Given that the basal forebrain plays a critical role in processes such as motivation, affect, and behavioral control, these findings support the hypothesis that nonserotonergic DRN projections may exert substantial modulatory control over emotional and motivational functions. Keywords amygdala; bed nucleus; 5,7-dihydroxytryptamine; septal nuclei; biotinylated dextran amine; tyrosine hydroxylase It is well known that the dorsal raphe nucleus contains more than half of all the serotonergic neurons in the brain (Leger and Wiklund, 1982) and is a source of projections that terminate extensively throughout the central nervous system (Vertes, 1991;Sim and Joseph, 1993;Vertes and Kocsis, 1994;Morin and Meyer-Bernstein, 1999 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. within dorsomedial (DRNdm), ventromedial (DRNvm), and lateral (DRNl) cell groups . It has been proposed that the activity of serotonergic DRN neurons plays an important role in the coordination of sensory processing and motor output with the sleep-wake-arousal cycle (Jacobs and Azmitia, 1992; Forn...

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Reciprocal connections between subdivisions of the dorsal raphe and the nuclear core of the locus coeruleus in the rat

Cited by 116 publications

References 55 publications

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Depression-like behavior in rat: Involvement of galanin receptor subtype 1 in the ventral periaqueductal gray

Urocortin 2-Deficient Mice Exhibit Gender-Specific Alterations in Circadian Hypothalamus–Pituitary–Adrenal Axis and Depressive-Like Behavior

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

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