Neuropeptide Y Produces Anxiety Via Y2-Type Receptors

doi:10.1016/S0196-9781(97)00298-2

Peptides

Volume 19, Issue 2, February 1998, Pages 359-363

https://doi.org/10.1016/S0196-9781(97)00298-2 Get rights and content

Abstract

Nakajima, M., A. Inui, A. Asakawa, K. Momose, N. Ueno, A. Teranishi, S. Baba and M. Kasuga. Neuropeptide Y produces anxiety via Y2-type receptors. Peptides 19(2) 359–363, 1998.—In the present study, the effects of intracerebroventricular (ICV) NPY, [Leu³¹, Pro³⁴]NPY and NPY_13–36 have been evaluated with respect to anxiety in mice in the elevated plus maze. NPY had opposing effects on behavior, depending on the doses used. NPY decreased the normal preference for the closed arms of the maze at 0.7 nmol, indicating an anxiolytic effect; however, at 7 pmol NPY further increased the preference for the closed arm, indicating an anxiogenic effect. [Leu³¹, Pro³⁴]NPY, a Y1-type receptor agonist, significantly reduced the preference for the closed arms at 70 pmol. NPY_13–36, a Y2-type receptor agonist, significantly intensified the preference at 20 pmol. It has been demonstrated that NPY produces not only an anxiolytic effect via Y1-type receptors, but also an anxiogenic effect via Y2-type receptors. The time course of these NPY actions are quite different and the anxiogenic effect was observed only shortly after ICV NPY injection.

Section snippets

Method

After 1 week of acclimation in the laboratory, male mice of the ddY strain (KEARI, Osaka, Japan), obtained at 7 weeks of age, were implanted with an ICV injection cannula and housed individually in a regulated environment (24 ± 2°C, 55 ± 10% humidity, 12-h light-dark cycle with light on 0700 h. The mice (n = 236) were used only once in the experiment. Water and food were available freely throughout the experiments.

As in previous studies 16, 22, 27, mice were anesthetized with pentobarbital

Results

The effects of NPY on anxiety and motor activity are shown in Fig. 1 and Table 1 respectively. ANOVA indicated significant peptide effects on % time [F(3, 54) = 14.488, p < 0.0001], % entry [F(3, 54) = 12.298, p < 0.0001] and total entry [F(3, 54) = 4.108, p < 0.05]. The subsequent analysis using Bonferroni’s t-test indicated that NPY significantly decreased % time at 7 pmol, and significantly increased both % time and % entry at 0.7 nmol, although 0.7 nmol of NPY significantly decreased

Discussion

In this study, NPY had an anxiolytic effect via Y1-type receptors at high doses (0.7 nmol/brain) as previously reported 12, 14, 28. On the other hand, it was also demonstrated that NPY produced anxiety via Y2-type receptors at low doses (7 pmol/brain). The anxiogenic effect was observed shortly after NPY administration and was no longer detected at 30 min after ICV injection; therefore, both the dose of NPY and the timing of behavioral testing may account for the differences in results.

The

Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research (C) 06671033 and for Developmental Scientific Research (B) 06557060 from the Ministry of Education, Science and Culture of Japan.

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Citation Excerpt :
Interestingly, Y1Rs and Y2Rs seem to exert opposing functional consequences in several brain areas. Intracerebroventricular infusion of Y1R agonist resulted in reduced anxiety levels while Y2R agonist infusion enhanced anxiety levels (Nakajima et al., 1998; Sajdyk et al., 2002). Overexpression of Y1Rs in the hippocampus or genetic deletion of Y2Rs in the central or basolateral amygdala (CeA or BLA) resulted in anxiolytic effects (Olesen et al., 2012; Tasan et al., 2010).
Neuropeptide Y (NPY) is one of peptide neuromodulators, well known for orexigenic, anxiolytic and antidepressant effects. We previously reported that NPY decreases GABAergic transmission in the lateral habenula (LHb). In the current study, we aim to investigate the underlying signaling pathways that mediate inhibitory action of NPY in the LHb by employing whole-cell patch clamp recording with pharmacological interventions. Here, we revealed that Y1 receptors (Y1Rs) but not Y2Rs mediate NPY-induced decrease of GABAergic transmission in the LHb. Surprisingly, NPY-induced decrease of inhibitory transmission in the LHb was not dependent on adenylyl cyclase (AC)/protein kinase A (PKA)-dependent pathway as reported in other brain areas. Instead, pharmacological blockade of phospholipase C (PLC) or protein kinase C (PKC) activity abolished the decrease of GABAergic transmission by NPY in the LHb. Our findings suggest that Y1Rs in the LHb may trigger the activation of PLC/PKC-dependent pathway but not the classical AC/PKA-dependent pathway to decrease inhibitory transmission of the LHb.

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ArticlesNeuropeptide Y Produces Anxiety Via Y2-Type Receptors

Abstract

Section snippets

Method

Results

Discussion

Acknowledgements

J. Biol. Chem.

TINS.

Brain. Res.

J. Biol. Chem.

Life Sci.

Brain Res.

J. Biol. Chem.

Regul. Pept.

J. Biol. Chem.

J. Neurosci. Methods

Regul. Pept.

Role of endogenous corticotropin-releasing factor in mediation of neuroendocrine and behavioral responses to cholecystokinin octapeptide sulfate ester in rats

Neuroendocrinology.

Chlordiazepoxide attenuates response suppression induced by corticotropin-releasing factor in the conflict test

Psychopharmacology.

Vasopressin mediates alpha 1-adrenergic stimulation of adrenocorticotropin secretion

Endocrinology.

Comparative characterization and autoradiographic distribution of neuropeptide Y receptor subtypes in the rat brain

J. Neurosci.

Articles
Neuropeptide Y Produces Anxiety Via Y2-Type Receptors