Galanin receptor/Neuropeptide Y receptor interactions in the dorsal raphe nucleus of the rat

Dı́az-Cabiale, Zaida; Parrado, Concepción; Narváez, Manuel; Puigcerver, Araceli; Millón, Carmelo; Santín, Luis J.; Fuxé, Kjell; Narváez, José Ángel

doi:10.1016/j.neuropharm.2011.03.002

Cited by 21 publications

(11 citation statements)

References 44 publications

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“…This rapid disappearance of the action at the higher concentration may reflect the depletion of a factor necessary for the formation of the GAL 1 and GAL 2 heteroreceptor complexes or the rapid development of a desensitisation mechanism at the GAL receptors. Similar biphasic concentration-response curves have also been observed for the GAL in its interaction with α2-adrenoreceptor ( Diaz-Cabiale et al, 2005 ) and with the neuropeptide Y ( Diaz-Cabiale et al, 2011 ).…”

Section: Discussionsupporting

confidence: 68%

“…This protocol has been used previously ( Parrado et al, 2007 ; Diaz-Cabiale et al, 2011 ). Briefly, the rats were anesthetized intraperitoneally with Equitesin (3.3mL/kg body weight), and stereotaxically implanted with a unilateral chronic 22-gauge stainless-steel guide cannula into the right lateral cerebral ventricle using the following coordinates: 1.4mm lateral and 1mm posterior to the bregma, and 3.6mm below the surface of the skull ( Paxinos, 1986 ).…”

Section: Methodsmentioning

confidence: 99%

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A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

Millón

Flores-Burgess

Narváez

et al. 2015

International Journal of Neuropsychopharmacology

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110

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Background:Galanin (GAL) plays a role in mood regulation. In this study we analyzed the action of the active N-terminal fragment [GAL(1–15)] in anxiety- and depression-related behavioral tests in rats.Methods:The effect of GAL(1–15) was analyzed in the forced swimming test, tail suspension test, open field test, and light/dark test. The proximity of GAL1 and GAL2 receptors was examined with the proximity ligation assay (PLA). We tested the GAL receptors involved in GAL(1–15) effects with the GAL2 receptor antagonist M871 and with an in vivo model of siRNA GAL2 receptor knockdown or siRNA GAL1 receptor knockdown rats. The effects of GAL(1–15) were also studied in the cell line RN33B.Results:GAL(1–15) induced strong depression-like and anxiogenic-like effects in all the tests. These effects were stronger than the ones induced by GAL. The involvement of the GAL2 receptor was demonstrated with M871 and with the siRNA GAL2 receptor knockdown rats. The PLA indicated the possible existence of GAL1 and GAL2 heteroreceptor complexes in the dorsal hippocampus and especially in the dorsal raphe nucleus. In the siRNA GAL1 receptor knockdown rats the behavioral actions of GAL(1–15) disappeared, and in the siRNA GAL2 receptor knockdown rats the reductions of the behavioral actions of GAL(1–15) was linked to a disappearance of PLA. In the cell line RN33B, GAL(1–15) decreased 5-HT immunoreactivity more strongly than GAL.Conclusions:Our results indicate that GAL(1–15) exerts strong depression-related and anxiogenic-like effects and may give the basis for the development of drugs targeting GAL1 and GAL2 heteroreceptor complexes in the raphe-limbic system for the treatment of depression and anxiety.

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Section: Discussionsupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

Millón

Flores-Burgess

Narváez

et al. 2015

International Journal of Neuropsychopharmacology

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110

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“…In a series of papers by Diaz-Cabiale and colleagues (Diaz-Cabiale et al, 2006, 2011; Parrado et al, 2007) evidence has been obtained for an antagonistic GalR modulation of NPY receptor mechanisms suggesting the existence of GALR–NPYY1 interactions involving a likely reduction of NPYY1 receptor agonist affinity probably taking place in GalR/NPYY1 receptor heteromers ( Figure 4A ) in NTS, hypothalamus, and DR (Diaz-Cabiale et al, 2006, 2011; Parrado et al, 2007). The results open up the possibility that GalR/NPYY1 receptor–receptor interactions in putative heteromers is a frequent phenomenon in CNS with implications for the integrative functions of galanin and NPY in these regions.…”

Section: Potential Existence Of Galr–npyy1 Receptor Heteromers In Thementioning

confidence: 98%

On the existence and function of galanin receptor heteromers in the central nervous system

Fuxé¹,

Borroto‐Escuela²,

Romero-Fernández³

et al. 2012

Front. Endocrin.

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Galanin receptor (GalR) subtypes 1–3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia–neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR–5-HT1A heteromers likely exist with antagonistic GalR–5-HT1A receptor–receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions. They represent a novel target for antidepressant drugs. Evidence is given for the existence of GalR1–5-HT1A heteromers in cellular models with trans-inhibition of the protomer signaling. A GalR1–GalR2 heteromer is proposed to be a galanin N-terminal fragment preferring receptor (1-15) in the CNS. Furthermore, a GalR1–GalR2–5-HT1A heterotrimer is postulated to explain why only galanin (1-15) but not galanin (1-29) can antagonistically modulate the 5-HT1A receptors in the dorsal hippocampus rich in gal fragment binding sites. The results underline a putative role of different types of GalR–5-HT1A heteroreceptor complexes in depression. GalR antagonists may also have therapeutic actions in depression by blocking the antagonistic GalR–NPYY1 receptor interactions in putative GalR–NPYY1 receptor heteromers in the CNS resulting in increases in NPYY1 transmission and antidepressant effects. In contrast the galanin fragment receptor (a postulated GalR1–GalR2 heteromer) appears to be linked to the NPYY2 receptor enhancing the affinity of the NPYY2 binding sites in a putative GalR1–GalR2–NPYY2 heterotrimer. Finally, putative GalR–α2-adrenoreceptor heteromers with antagonistic receptor–receptor interactions may be a widespread mechanism in the CNS for integration of galanin and noradrenaline signals also of likely relevance for depression.

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“…In our study, the non-principal neurons are the inhibitory GABAergic and excitatory glutamatergic neurons, although there exist other neuronal types (e.g. neurons containing neuropeptide Y, etc) [87].…”

Section: Discussionmentioning

confidence: 88%

Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

et al. 2014

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Orexinergic/hypocretinergic (Ox) neurotransmission plays an important role in regulating sleep, as well as in anxiety and depression, for which the serotonergic (5-HT) system is also involved in. However, little is known regarding the direct and indirect interactions between 5-HT in the dorsal raphe nucleus (DRN) and Ox neurons in the lateral hypothalamus (LHA). In this study, we report the additional presence of 5-HT1BR, 5-HT2AR, 5-HT2CR and fast ligand-gated 5-HT3AR subtypes on the Ox neurons of transgenic Ox-enhanced green fluorescent protein (Ox-EGFP) and wild type C57Bl/6 mice using single and double immunofluorescence (IF) staining, respectively, and quantify the colocalization for each 5-HT receptor subtype. We further reveal the presence of 5-HT3AR and 5-HT1AR on GABAergic neurons in LHA. We also identify NMDAR1, OX1R and OX2R on Ox neurons, but none on adjacent GABAergic neurons. This suggests a one-way relationship between LHA’s GABAergic and Ox neurons, wherein GABAergic neurons exerts an inhibitory effect on Ox neurons under partial DRN’s 5-HT control. We also show that Ox axonal projections receive glutamatergic (PSD-95 immunopositive) and GABAergic (Gephyrin immunopositive) inputs in the DRN. We consider these and other available findings into our computational model to explore possible effects of neural circuit connection types and timescales on the DRN-LHA system’s dynamics. We find that if the connections from 5-HT to LHA’s GABAergic neurons are weakly excitatory or inhibitory, the network exhibits slow oscillations; not observed when the connection is strongly excitatory. Furthermore, if Ox directly excites 5-HT neurons at a fast timescale, phasic Ox activation can lead to an increase in 5-HT activity; no significant effect with slower timescale. Overall, our experimental and computational approaches provide insights towards a more complete understanding of the complex relationship between 5-HT in the DRN and Ox in the LHA.

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Galanin receptor/Neuropeptide Y receptor interactions in the dorsal raphe nucleus of the rat

Cited by 21 publications

References 44 publications

A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

A Role for Galanin N-Terminal Fragment (1–15) in Anxiety- and Depression-Related Behaviors in Rats

On the existence and function of galanin receptor heteromers in the central nervous system

Neural Circuit Interactions between the Dorsal Raphe Nucleus and the Lateral Hypothalamus: An Experimental and Computational Study

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