We analyzed the modulation of calcitonin gene-related peptide (CGRP; exerting anxiogenic effects in BNST), neuropeptide Y (NPY; exerting mainly anxiolytic effects), and microglia activation (neuroinflammation marker, thought to increase anxiety).
However, genetic mouse models in combination with novel neuron-controlling chemogenetic and optogenetic technologies have also uncovered additional functions for this Arc NPY population that go beyond the simple food intake stimulatory action and link these NPY neurons to the control of energy expenditure, thermogenesis, physical activity, food-seeking behavior, and anxiety.
Our findings support the conclusion that alterations in both hippocampal NPY and MC4R expression are involved in anxiety level changes in rats, while their quantitative relationship (NPY/MC4R ratio) is even more valuable in the estimation of anxiety regulation than individual alterations for both NPY and MC4R expression in the hippocampus.
Although NPY has potent anxiolytic actions within the BLA, selective activation of BLA NPY Y<sub>2</sub> receptors (Y<sub>2</sub>Rs) acutely increases anxiety by an unknown mechanism.
Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology <sup>1,2</sup> .
By demonstrating that NPY release modulates hippocampal synaptic plasticity and is impaired by predator scent stress, our results provide a novel mechanism by which stress-induced anxiety alters circuit function.
In this review, we present an overview of findings with regard to the NPY system in relation to anxiety and stress, acute as well as chronic; furthermore we discuss post-traumatic stress disorder and, in part depression.
Several reports have demonstrated that neuropeptide Y (NPY) is involved in food intake, epilepsy, circadian rhythms, drug seeking, pain and anxiety, and other physiological or pathological conditions.
Increased melanocortin and decreased neuropeptide Y activity due to changes in histone acetylation in emotional brain circuitry may play a role in adolescent intermittent ethanol-induced anxiety phenotypes in adulthood.
NPY has recently gained much attention as an endogenous antiepileptic and antidepressant agent, as drugs with antiepileptic and/or mood-stabilizing properties may exert their action by increasing NPY concentrations, which in turn can reduce anxiety and depression levels, dampen seizures or increase seizure threshold.
However, alterations in anxiety- and depression-regulating genes were present in the hypothalamus of BACHD mice including reduced mRNA expression of neuropeptide Y, tachykinin receptor 3 and vesicular monoamine transporter type 2 as well as increased expression of cocaine and amphetamine regulated transcript.
CCK interacts with several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and noradrenergic system as well as with endocannabinoids, NPY and NPS.
We additionally found that SNPs and haplotypes in neuropeptide Y (NPY) modified the effect of childhood adversities on anxiety susceptibility (P = 0.003).
This differential genetic modulation of NPY stress response was suppressed in the SD group, who showed no stress-related increases in NPY and higher heart rate and greater anxiety, regardless of diplotype.
There is extensive evidence, from both clinical cases and rodent models, for reduced levels of the widely expressed neuropeptide Y (NPY) in anxiety and depressive disorders.
Here we show that the claims of Zhou et al. that neuropeptide Y (NPY) diplotype-predicted expression is correlated with trait anxiety (neuroticism) is not replicated in a data set consisting of phenotypically extreme individuals drawn from a large (n = 88,142) non-clinical population.
Since the neuropeptide Y (NPY) system has been reported to be involved in the pathophysiology of anxiety and in particular panic disorder and the genes coding for NPY Y1, Y2, and Y5 receptors are located in the suggested risk region (4q31-q32), variants in the NPY, NPY Y1, Y2, and Y5 genes were investigated for association with panic disorder in a sample of 230 German patients with panic disorder and matched healthy controls.