Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique

Aghajanian, G K; Wang, Rex Y.

doi:10.1016/0006-8993(77)90291-8

Cited by 360 publications

(120 citation statements)

References 29 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%

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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%

“…With regard to descending systems, a glutamatergic projection from the forebrain (medial prefrontal cortex/hippocampus) to the vPAG/DR is well established (121,(143)(144)(145)(146)(147)(148)(149)(150). In agreement, VGLUT1 + and VGLUT2 + boutons synapse both on TPH + and TPH − neurons (151).…”

Section: Discussionmentioning

confidence: 99%

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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“…Consistent with this hypothesis, it has been demonstrated that rat medial prefrontal cortex (prelimbic area) has dense efferent projections to both the dorsal and the median raphe nuclei (Aghajanian and Wang 1977;Beckstead 1979;Wyss and Sripanidkulchai 1984;Sesack et al 1989;Behzadi et al 1990;Peyron et al 1998). Thus, it is possible that PFC stimulation activates the raphe nuclei leading to increased -HT levels in terminal areas.…”

Section: Discussionmentioning

confidence: 64%

“…Stimulation of such cortical areas outside the PFC as the medial precentral area Fr2, the primary motor, and the parietal cortex did not affect serotonin output in either hippocampus or amygdala. One possible explanation for this is that the prefrontal cortex is the only cortical area with direct projections to the midbrain raphe nuclei in rats (Aghajanian and Wang 1977;Behzadi et al 1990;Marcinkiewicz et al 1989;Peyron et al 1998), as well as in primates (Arnsten and GoldmanRakic 1984). It is noteworthy that there is still open debate as to whether the medial precentral area Fr2, located in the dorsomedial, or so-called shoulder region of the rat frontal cortex, belongs to the PFC (Uylings and Van Eden 1990;Preuss 1995).…”

Section: Discussionmentioning

confidence: 99%

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

Juckel

1999

Neuropsychopharmacology

103

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Decreased activity of the prefrontal cortex (PFC), as well as reduced serotonergic neurotransmission, is considered as a characteristic feature of major depression. The mechanism by which electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) achieve their antidepressant effects may involve changes in PFC activity. It is, however, still unclear whether these changes are accompanied by increased synaptic availability of serotonin (5-HT). In the present study, 5-HT efflux in the rat ventral hippocampus and amygdala was analyzed using in vivo microdialysis during low-current electrical stimulation of PFC and other cortical regions. Electrical stimulation of the medial PFC produced current-dependent increases in limbic 5-HT output in both urethane-anesthetized and behaving rats. No effects on 5-HT levels were seen after comparable stimulation of either the lateral parts of the PFCAn extensive body of clinical evidence suggests that prefrontal cortex (PFC) abnormalities are involved in the pathophysiology of major depression. Significantly decreased cerebral blood flow as well as reduced rates of glucose metabolism have been consistently found in the PFC of depressed patients (Soares and Mann 1997;Kennedy et al. 1997;George et al. 1993). This reduction seems to be localized predominantly in the left hemisphere (Baxter et al. 1989;Martinot et al. 1990). This is supported by structural neuroimaging studies demonstrating that poststroke depression is more likely to occur following a lesion in the left PFC rather than either in the right PFC or elsewhere in the left hemisphere (Morris et al. 1996;Robinson et al. 1984). Both neuropsychological and oculomotor functioning of prefrontal cortex is impaired in depression (Goodwin 1997;Sweeney et al. 1998). Furthermore, symptom improvement and remission of depressed patients have been associated with increases in cerebral blood flow and glucose metabolism in this region (Goodwin et al. 1993;Bench et al. 1995;Bonne and Krausz 1997;Buchsbaum et al. 1997 NO . 3 This close association between prefrontal cortical dysfunction and depression suggests that enhancement of PFC activity might be beneficial in the treatment of this disorder. Consistent with this idea, electroconvulsive therapy (ECT), as well as transcranial magnetic stimulation (TMS), seems to achieve its antidepressant effects by altering PFC activity. ECT leads to pronounced prefrontal EEG changes, which are directly related to the therapeutic outcome. Hence, the efficacy of ECT seems to be critically linked to prefrontal cortex involvement in ECT-induced seizure activity (Sackeim et al. 1996). This is further supported by studies that have reported changes in cerebral blood flow in prefrontal cortex of ECT responders (Nobler et al. 1994;Bonne et al. 1996;Petracca et al. 1995). In recent years, repetitive TMS of the left dorsolateral prefrontal cortex has emerged as a successful antidepressant treatment (Pascual-Leone et al. 1996;George et al. 1997). Although the exact mechanism underlying the ef...

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“…Among these, the catecholamine groups (Baraban and Aghajanian, 1980;Peyron et al, 1996), the lateral habenula (Aghajanian and Wang, 1977;Stern et al, 1981), and the medial prefrontal cortex (Aghajanian and Wang, 1977;Sesack et al, 1989;Hajós et al, 1998;Peyron et al, 1998;Celada et al, 2001;Martín-Ruiz et al, 2001a) play a major role.…”

Section: Introductionmentioning

confidence: 99%

Control of 5-Hydroxytryptamine Release in the Dorsal Raphe Nucleus by the Noradrenergic System in Rat Brain. Role of α-Adrenoceptors

Bortolozzi

Artigas

2002

Neuropsychopharmacol

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The interactions between the brainstem serotonergic (5-hydroxytryptamine, 5-HT) and noradrenergic (NA) systems are important for the pathophysiology and treatment of affective disorders. We examined the influence of a-adrenoceptors on 5-HT and NA release in the rat dorsal raphe nucleus (DR) using microdialysis. 5-HT and NA concentrations in DR dialysates were virtually suppressed by TTX and increased by veratridine. The local and systemic administration of the a 1 -adrenoceptor antagonist prazosin reduced the DR 5-HT output but not that of NA. The maximal 5-HT reduction induced by local prazosin administration (À78% at 100 mM) was more marked than by its systemic administration (À43% at 0.3 mg/kg). The local application of NA and desipramine, to increase the tone on DR a 1 -adrenoceptors, did not enhance 5-HT release. The local (100 mM) or systemic (0.1-1 mg/kg s.c.) administration of clonidine reduced 5-HT and NA release (À48 and À79%, respectively, at 1 mg/kg), an effect reversed by RX-821002, which by itself increased both amines when given systemically. DSP-4 pretreatment prevented the effects of clonidine on 5-HT, suggesting the participation of a 2 -adrenoceptors on NA elements. Moreover, the systemic effect of clonidine on 5-HT (but not NA) was cancelled by lesion of the lateral habenula and by anesthesia, and was slightly enhanced by cortical transection. These data support the view that a 1 -adrenoceptors in the DR tonically stimulate 5-HT release, possibly at nearly maximal tone. Likewise, the 5-HT release is modulated by a 2 -adrenoceptors in NA neurons and in forebrain areas involved in the distal control of 5-HT neurons.

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Habenular and other midbrain raphe afferents demonstrated by a modified retrograde tracing technique

Cited by 360 publications

References 29 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

Electrical Stimulation of Rat Medial Prefrontal Cortex Enhances Forebrain Serotonin Output Implications for Electroconvulsive Therapy and Transcranial Magnetic Stimulation in Depression

Control of 5-Hydroxytryptamine Release in the Dorsal Raphe Nucleus by the Noradrenergic System in Rat Brain. Role of α-Adrenoceptors

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