Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze

Britton, Karen T.; Akwa, Yvette; Spina, Mariarosa; Koob, George F.

doi:10.1016/s0196-9781(99)00169-2

Cited by 92 publications

(53 citation statements)

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“…The release of NPY is thought to facilitate the containment of negative consequences following exposure to stress and has anxiolytic-like effects (Heilig, 2004). Intracerebroventricular administration of NPY or NPY-Y1-receptor agonists decrease anxiety-related behaviors in the Geller-Seifter conflict test, fear potentiated startle test, and the elevated plus maze (EPM) test, without altering locomotor activity (Britton et al, 1997(Britton et al, , 2000Broqua et al, 1995;Heilig et al, 1989;Primeaux et al, 2005). Intracerebroventricular administration of antisense oligonucleotides for the NPY-Y1 receptor or the non-peptide NPY-Y1-receptor antagonist (Y1RA), BIBP3226, increases anxiety-related behaviors in the EPM test (Kask et al, 1996;Wahlestedt et al, 1993).…”

Section: Introductonmentioning

confidence: 99%

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Cohen

Liu

Kozlovsky

et al. 2011

Neuropsychopharmacol

235

190

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Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety-and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery.

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Section: Introductonmentioning

confidence: 99%

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Cohen

Liu

Kozlovsky

et al. 2011

Neuropsychopharmacol

235

190

View full text Add to dashboard Cite

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“…) administration of NPY or NPY Y1 receptor agonists decrease anxiety-related behaviors in the Geller-Seifter conflict test, fear potentiated startle test, and the elevated plus maze test, without altering locomotor activity. (Britton et al, 1997(Britton et al, , 2000Broqua et al, 1995;Heilig et al, 1989;Nakajima et al, 1998). In contrast, NPY Y2 receptor agonists decrease the percent time spent in the open arms of the plus maze, which is indicative of increased levels of anxiety (Nakajima et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

“…This neuropeptide is found in cortical structures, the ventral and dorsal striatum, limbic structures, and brain stem, and is often colocalized with norepinephrine and gammaaminobutyric acid as well as other neuropeptides (Heilig and Widerlov, 1990;Kask et al, 2002). NPY plays a role in anxiety (Britton et al, 1997(Britton et al, , 2000Broqua et al, 1995;Heilig et al, 1993;Pich et al, 1993;Sajdyk et al, 1999), depression (Holmes et al, 1998;Jimenez-Vasquez et al, 2000Song et al, 1996;Stogner and Holmes, 2000;Widerlov et al, 1988), feeding (Daniels et al, 2001;Flood and Morley, 1991;Heilig et al, 1993;Mullins et al, 2001;Polidori et al, 2000), and seizure activity (Baraban et al, 1997;Erickson et al, 1996;Vezzani et al, 2002;Weinshenker et al, 2001;Woldbye et al, 1996Woldbye et al, , 1997.…”

Section: Introductionmentioning

confidence: 99%

Effects of Altered Amygdalar Neuropeptide Y Expression on Anxiety-Related Behaviors

Primeaux

Wilson

Cusick

et al. 2005

Neuropsychopharmacol

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Neuropeptide Y (NPY) decreases anxiety-related behaviors in various animal models of anxiety. The purpose of the present study was to examine the role of the amygdalar NPY system in anxiety-related responses in the elevated plus maze. The first experiment determined if herpes virus-mediated alterations in amygdalar NPY levels would alter anxiety-related behaviors in the elevated plus maze. Viral vectors encoding NPY, NPY antisense, or LacZ (control virus) were bilaterally injected into the amygdala, and 4 days postinjection, rats were tested in the elevated plus maze test. NPY-like immunoreactivity (NPY-ir) was measured in the amygdala of these rats. In rats injected with the viral vector encoding NPY, reduced anxiety-related behaviors in the elevated plus maze accompanied by moderate increases in NPY-ir were detected compared to NPY-antisense viral vector-treated subjects. Elevated plus maze behavior did not differ compared to LacZ-treated controls. NPY overexpression at this time point was also suggested by enhanced NPY mRNA expression seen in the amygdala 4 days postinjection using real-time polymerase chain reaction analysis. Experiment 2 was conducted to provide further evidence for a role of amygdalar NPY in regulating anxiety-related behaviors in the elevated plus maze test. The nonpeptide NPY Y1 receptor antagonist, BIBP 3226 (1.5 mg/ml), was bilaterally injected into the amygdala and rats were tested in the elevated plus maze test. Rats receiving BIBP 3226 exhibited increased anxiety-related behaviors in this test. The results of these experiments provide further support for the role of amygdalar NPY in anxiety-related behaviors. Neuropsychopharmacology (2005) 30, 1589-1597.

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“…The pharmacological administration of NPY into the CNS induces anxiolytic effects in various animal models (Heilig et al 1989;Bannon et al 2000;Thorsell et al 2000;Kask et al 2001) and antagonizes the anxiogenic-like action of corticotropin-releasing factor (CRF) in the elevated plus maze (Britton et al 2000). Five receptor subtypes for NPY have been identified and termed Y 1 , Y 2 , Y 4 , Y 5 and Y 6 (Michel et al 1998).…”

mentioning

confidence: 99%

Increased expression of the gene for the Y₁ receptor of neuropeptide Y in the amygdala and paraventricular nucleus of Y₁R/LacZ transgenic mice in response to restraint stress

Marrama

Oberto

Serra

et al. 2004

Journal of Neurochemistry

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A sustained increase in the brain concentrations of neuroactive steroids was previously shown to induce Y 1 receptor gene expression in the amygdala of Y 1 R/LacZ transgenic mice which harbour a construct comprising the murine Y 1 receptor gene promoter and the lacZ reporter gene. We now investigated the effects of restraint stress on both the cerebrocortical concentrations of neuroactive steroids and Y 1 receptor gene expression in the amygdala and hypothalamic paraventricular nucleus (PVN) of Y 1 R/LacZ transgenic mice. The cerebrocortical concentrations of allopregnanolone and allotetrahydrodeoxycorticosterone were significantly increased immediately after a 1-h exposure to restraint stress and had returned to control values within 30 min. Expression of Y 1 R/LacZ was increased in the amygdala and PVN 6 h after restraint. The 5a-reductase inhibitor finasteride, that prevented the increase in neuroactive steroid concentrations, did not block that in transgene expression induced by 1-h restraint. Daily exposure to restraint for 10 days also increased the cerebrocortical concentrations of neuroactive steroids but failed to affect transgene expression. Neuropeptide Y (NPY) is a 36-amino acid neurotransmitter that participates in the control of food intake, cerebrocortical excitability, cardiovascular homeostasis, the behavioural response to stressful stimuli and emotional behaviour (Kask et al. 2002;Malmstrom 2002;Parker et al. 2002). The pharmacological administration of NPY into the CNS induces anxiolytic effects in various animal models (Heilig et al. 1989;Bannon et al. 2000;Thorsell et al. 2000;Kask et al. 2001) and antagonizes the anxiogenic-like action of corticotropin-releasing factor (CRF) in the elevated plus maze (Britton et al. 2000).

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Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze

Cited by 92 publications

References 50 publications

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Effects of Altered Amygdalar Neuropeptide Y Expression on Anxiety-Related Behaviors

Increased expression of the gene for the Y₁ receptor of neuropeptide Y in the amygdala and paraventricular nucleus of Y₁R/LacZ transgenic mice in response to restraint stress

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Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze

Cited by 92 publications

References 50 publications

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

Effects of Altered Amygdalar Neuropeptide Y Expression on Anxiety-Related Behaviors

Increased expression of the gene for the Y1 receptor of neuropeptide Y in the amygdala and paraventricular nucleus of Y1R/LacZ transgenic mice in response to restraint stress

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Product

Resources

About

Increased expression of the gene for the Y₁ receptor of neuropeptide Y in the amygdala and paraventricular nucleus of Y₁R/LacZ transgenic mice in response to restraint stress