Interactions between NPY and CRF in the amygdala to regulate emotionality

Sajdyk, Tammy J.; Shekhar, Anantha; Gehlert, Donald R.

doi:10.1016/j.npep.2004.05.006

Cited by 167 publications

(126 citation statements)

References 82 publications

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“…In this regard, NPY has a reciprocal functional relationship with both norepinephrine (15) and corticotropin-releasing hormone (CRH) (16). Interestingly, our previous data showing elevated basal CRH and norepinephrine concentrations in the CSF of combat-related PTSD patients (17,18) are consistent with the current finding.…”

Section: Discussionsupporting

confidence: 92%

Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder

Sah

Ekhator

Strawn

et al. 2009

Biological Psychiatry

132

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Section: Discussionsupporting

confidence: 92%

Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder

Sah

Ekhator

Strawn

et al. 2009

Biological Psychiatry

132

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“…These dual effects of a Y 1 R agonist in combination would increase overall inhibition of BLA glutamatergic pyramidal neurons and would be consistent with anxiolytic behavior. Previous findings in our lab and others support the hypothesis that NPY in the BLA exerts an anxiolytic effect (Karlsson et al, 2008;Sajdyk et al, 2004Sajdyk et al, , 2006Wahlestedt and Reis, 1993b). Furthermore, for the first time we demonstrate that the activation of Y 1 Rs decreases NMDA-mediated currents, an important new finding with implications for the role of NPY in modulating not only excitability but also synaptic plasticity within the BLA.…”

Section: Implications Of Y 1 R-mediated Increases Of Gaba a -Mediatedsupporting

confidence: 87%

NPY Y1 Receptors Differentially Modulate GABAA and NMDA Receptors via Divergent Signal-Transduction Pathways to Reduce Excitability of Amygdala Neurons

Molosh

Sajdyk

Truitt

et al. 2013

Neuropsychopharmacol

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Neuropeptide Y (NPY) administration into the basolateral amygdala (BLA) decreases anxiety-like behavior, mediated in part through the Y 1 receptor (Y 1 R) isoform. Activation of Y 1 Rs results in G-protein-mediated reduction of cAMP levels, which results in reduced excitability of amygdala projection neurons. Understanding the mechanisms linking decreased cAMP levels to reduced excitability in amygdala neurons is important for identifying novel anxiolytic targets. We studied the intracellular mechanisms of activation of Y 1 Rs on synaptic transmission in the BLA. Activating Y 1 Rs by [Leu 31 ,Pro 34 ]-NPY (L-P NPY) reduced the amplitude of evoked NMDA-mediated excitatory postsynaptic currents (eEPSCs), without affecting AMPA-mediated eEPSCs, but conversely increased the amplitude of GABA A -mediated evoked inhibitory postsynaptic currents (eIPSCs). Both effects were abolished by the Y 1 R antagonist, PD160170. Intracellular GDP-b-S, or pre-treatment with either forskolin or 8Br-cAMP, eliminated the effects of L-P NPY on both NMDA-and GABA A -mediated currents. Thus, both the NMDA and GABA A effects of Y 1 R activation in the BLA are G-protein-mediated and cAMPdependent. Pipette inclusion of protein kinase A (PKA) catalytic subunit blocked the effect of L-P NPY on GABA A -mediated eIPSCs, but not on NMDA-mediated eEPSCs. Conversely, activating the exchange protein activated by cAMP (Epac) with 8CPT-2Me-cAMP blocked the effect of L-P NPY on NMDA-mediated eEPSCs, but not on GABA A -mediated eIPSCs. Thus, NPY regulates amygdala excitability via two signal-transduction events, with reduced PKA activity enhancing GABA A -mediated eIPSCs and Epac deactivation reducing NMDAmediated eEPSCs. This multipathway regulation of NMDA-and GABA A -mediated currents may be important for NPY plasticity and stress resilience in the amygdala.

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“…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).…”

mentioning

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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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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Interactions between NPY and CRF in the amygdala to regulate emotionality

Cited by 167 publications

References 82 publications

Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder

Low Cerebrospinal Fluid Neuropeptide Y Concentrations in Posttraumatic Stress Disorder

NPY Y1 Receptors Differentially Modulate GABAA and NMDA Receptors via Divergent Signal-Transduction Pathways to Reduce Excitability of Amygdala Neurons

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

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