P.4.b.006 Interpreting the social scene: threat detection and cost attribution in social anxiety
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Dorsal raphe nucleus
Periaqueductal gray
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Escape response
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Recent neurochemical studies of the properties of 5-hydroxytryptamine (5-HT) pathways arising from the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN) have measured extracellular 5-HT in brain regions with reported preferential DRN or MRN 5-HT inputs. Here, we have tested whether electrical stimulation of the DRN and MRN releases 5-HT in rat forebrain regions in a pattern that fits the reported distribution of DRN/MRN pathways. The effect on extracellular 5-HT of electrical stimulation (5 Hz, 300 microA, 20 min) of the DRN, and then MRN, was determined in six regions of the anaesthetised rat. Stimulation of the DRN evoked a short-lasting but clear-cut release of 5-HT (+70-100%) in regions (frontal cortex, dorsal striatum, globus pallidus, and ventral hippocampus) reported to receive a 5-HT projection from the DRN. Regions receiving an MRN innervation (dorsal hippocampus, medial septum, and ventral hippocampus) released 5-HT (+70-100%) in response to MRN stimulation. Regions reported to receive a preferential DRN innervation (frontal cortex, dorsal striatum, and globus pallidus) did not respond to MRN stimulation. Of two regions (dorsal hippocampus and medial septum) reported to receive a preferential MRN innervation, one did not respond to DRN stimulation (dorsal hippocampus) although the other (medial septum) did. In summary, electrical stimulation of the DRN and MRN released 5-HT in a regionally specific pattern. With the exception of one region (medial septum), this pattern of release bears a strong relationship to the distribution of 5-HT projections from the DRN and MRN reported by anatomical studies. The combination of raphe stimulation with microdialysis may be a useful way to study the in vivo neurochemistry of DRN/MRN 5-HT pathways.
Dorsal raphe nucleus
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Medial forebrain bundle
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5-HT4 receptor
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Median raphe nucleus
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Abstract: Extracellular 5‐hydroxytryptamine (5‐HT) in the median raphe and dorsal hippocampus was measured using in vivo microdialysis. Administration of 60 m M K + through the probe into the median raphe region significantly increased 5‐HT output from the median raphe and the right dorsal hippocampus. Local infusion of 10 µ M tetrodotoxin into the median raphe region substantially decreased 5‐HT in the median raphe and left and right dorsal hippocampus. Systemic administration (0.3 mg/kg s.c.) of 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin (8‐OH‐DPAT) decreased the 5‐HT levels in the dialysates from both the median raphe region and dorsal hippocampus. Administration of 30 n M 8‐OH‐DPAT through the dialysis probe into the median raphe region decreased 5‐HT output from the median raphe and dorsal hippocampus significantly, whereas at concentrations from 60 n M to 10 µ M , no significant effects were found in either region. With 100 µ M 8‐OH‐DPAT, a significant increase was seen in the median raphe region, but not in dorsal hippocampus. Similar findings were obtained following microinjections of different doses of the compound into the median raphe region. The results of this study indicate that the somatodendritic release of 5‐HT is impulse flow‐dependent. Moreover, the decrease of 5‐HT in the median raphe region by low nanomolar concentrations of 8‐OH‐DPAT supports the notion that somatodendritic 5‐HT release is subject to a local negative feedback mechanism through 5‐HT 1A autoreceptors.
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Abstract The binding of 3 H‐CN‐IMI to 5‐HT uptake sites, as measured by quantitative autoradiography, was used as a marker of serotonergic neurons. Within the dorsal raphe nucleus the binding of 3 H‐CN‐IMI was compared in adjacent coronal sections of rat brain to the binding of 3 H‐DPAT to 5‐HT 1A receptors, which have a known somatodendritic localization. The heterogeneous pattern of binding of these two radioligands within the dorsal raphe nucleus was similar and corresponded to the distribution of serotonergic cell bodies as visualized by 5‐HT immunohistochemistry. Intracerebroventricular administration of 5,7‐dihydroxytryptamine (5,7‐DHT), which caused a dramatic loss of 5‐HT immunoreactivity and 3 H‐DPAT binding to 5‐HT 1A receptors, resulted in a marked reduction of 3 H‐CN‐IMI binding in this nucleus. Treatment of rats with a dose of parachloroamphetamine (PCA) which has been reported to selectively lesion serotonergic processes arising from the dorsal raphe nucleus, while sparing serotonergic cell bodies and projections from the median raphe nucleus, did not alter the binding of 3 H‐DPAT or 3 H‐CN‐IMI in the dorsal raphe nucleus; serotonergic cell bodies appeared morphologically unaffected. The lack of effect of PCA treatment on the binding of 3 H‐DPAT and 3 H‐CN‐IMI is consistent with a somatodendritic localization of the 5‐HT transporter in the dorsal raphe nucleus. PCA treatment appeared to produce a moderate loss of serotonergic innervation in serotonergic terminal field areas as visualized by serotonin immunohistochemistry. The reductions in 3 H‐CN‐IMI binding observed in terminal field areas (24 to 69%) following treatment of rats with PCA did not reflect a marked differential innervation of forebrain areas by the dorsal and medial raphe nuclei as expected from previous biochemical studies, and were not entirely consistent with the findings of neuroanatomical studies using histochemical techniques. Site‐specific injection of 5,7‐DHT into the dorsal raphe nucleus produced an 80 ± 11% reduction in the binding of 3 H‐CN‐IMI in this nucleus, whereas the binding of 3 H‐CN‐IMI in the median raphe nucleus was not reduced. The reductions in 3 H‐CN‐IMI binding measured in the caudate putamen, frontal and entorhinal cortex as a result of specific lesion of the dorsal raphe nucleus were suggestive of a heavy innervation of these areas by the dorsal raphe nucleus as indicated in neuroanatomical studies. In the hippocampus, our data were consistent with an overlapping innervation of these areas by both the dorsal and median raphe nuclei and are not reflective of predominantt innervation by the medial raphe nucleus. © 1994 Wiley‐Liss, Inc.
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The effect of lesion of the dorsal raphe nucleus (DRN) or median raphe nucleus (MRN) on the locomotor activity, open field performance, and reactivity to noxious stimulus was tested in rats. During the first 7 days after the lesion, the rats with lesioned DRN showed higher basal and explorative locomotor activity than the rats with MRN lesions. The lesion of DRN increased the open-field performance and reactivity to pain. The results of tests carried out on the rats with MRN lesions were similar as in control rats. The results indicate that the different behavioral effect of lesions of DRN and MRN reffects differences in the functions of these two raphe nuclei.
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