Journal
JOURNAL OF NEUROSCIENCE RESEARCH
Volume 81, Issue 4, Pages 488-496Publisher
WILEY
DOI: 10.1002/jnr.20571
Keywords
nociceptin; dorsal raphe nucleus; G-proteins; serotonin; ORL1 (NOP) receptor
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A high density of opioid receptor-like 1 (ORL1) receptor (also referred to as NOP receptor) is found in limbic areas and in regions containing monoamines, which are implicated in emotional activity and physiopathology of depression and anxiety. We aimed at defining precisely the localization of ORL1 receptors in dorsal raphe nucleus, by means of a lesion strategy and autoradiographic studies. In control rats, [H-3]nociceptin and nociceptin-stimulated [S-35]GTP gamma S bindings were found to be correlated in several brain regions. We performed in rats a selective destruction of serotoninergic neurons by surgical stereotaxic injection of 5,7-dihydroxytrypt-amine (5,7-DHT) in dorsal raphe nucleus. This led to a marked decrease in serotonin contents in striata and frontal cortices (about -60%) and in autoradiographic [H-3]citalopram binding in posterior regions. In dorsal raphe nucleus, [H-3]nociceptin binding was decreased to the same extent as [H-3]citalopram binding, whereas it was unchanged in the other regions studied. Nevertheless, in the dorsal raphe, nociceptin-stimulated [S-35]GTP gamma S binding was decreased to a lesser extent than [H-3]nociceptin binding in 5,7-DHT-lesioned rats. The ratio between nociceptin-stimulated [S-35]GTP gamma S binding and [H-3]nociceptin binding was significantly increased in 5,7-DHT-lesioned rats compared with controls in this region. These data demonstrate 1) that ORL1 receptors are located on serotoninergic neurons in the dorsal raphe nucleus and 2) that, after a lesion, the functionality of remaining ORL1 receptors appears to be up-regulated, which could correspond to a compensatory mechanism. (c) 2005 Wiley-Liss, Inc.
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