Anxiolytic-like effect of neuropeptide Y (NPY) and NPY13–36 microinjected into vicinity of locus coeruleus in rats

Kask, Ants; Rägo, Lembit; Harro, Jaanus

doi:10.1016/s0006-8993(98)00076-6

Cited by 91 publications

(46 citation statements)

References 26 publications

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“…Behavioral tests were performed in males, due to fluctuations in sex hormones during the ovarian cycle in females affecting their behavior. In these tests, OE-NPY DBH mice showed a tendency towards anxiolytic behavior when compared with wild-type mice, which is in agreement with several previous preclinical studies where increased NPY levels have been shown to reduce anxiety especially in the area of the amygdala and the brainstem [11, 13, 27, 28]. Some clinical studies also suggest that high plasma NPY may predict better coping with stress and less vulnerability to PTSD in combat exposed soldiers [6, 7].…”

Section: Discussionsupporting

confidence: 90%

“…The effects of both stressors on NPY release as well as levels of corticosterone as a measure of HPA axis upregulation were measured. Since NPY in the amygdala [11, 12] and in the brainstem [13] have been shown to reduce anxiety in vivo, we performed a range of neurobehavioral screening tests to assess the possible phenotype differences between OE-NPY DBH and wild-type mice that could effect the stress responses.…”

Section: Introductionmentioning

confidence: 99%

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Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

et al. 2008

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Background and Aims: Neuropeptide Y (NPY) is a sympathetic neurotransmitter co-stored and co-released with noradrenaline and adrenaline. We have constructed a novel NPY transgenic mouse model (OE-NPY^DBH mouse) where targeted overexpression results in increased levels of NPY in the brainstem and adrenal glands. The present study was aimed to understand the role of NPY released from sympathetic nerves and brain noradrenergic neurons in regulation of blood pressure, and behavioral responses to stress. Methods: Blood pressure was measured by radiotelemetry in conscious male OE-NPY^DBH and wild-type mice during surgical stress and in baseline conditions. Plasma and adrenal gland catecholamine levels were measured at baseline. Acute immobilization and cold exposure were used to study the plasma levels of NPY and corticosterone in stress, and brown adipose tissue thermogenic activity was measured with [³H]GDP binding after cold. Results: Here, we demonstrate that sympathoadrenal activity is enhanced in the OE-NPY^DBH mice. Blood pressure during surgical stress was significantly increased in comparison with wild-type controls. Furthermore, OE-NPY^DBH mice showed sexually dimorphic NPY responses to stress, and an anxiolytic-like behavior in elevated plus-maze and light-dark tests. Conclusion: This study shows that the overactive noradrenergic NPY system plays a role in regulation of blood pressure and adaptive responses to stress, and may be a link between chronic stress and adiposity-associated disturbances in metabolism.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

et al. 2008

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“…Although other studies have indicated that centrally administered NPY has anxiolytic-like effects in the EPM (Broqua et al, 1995;Heilig, 1995;Kask et al, 1998), it appears that the doses of NPY were either 10-fold greater than what was used in the current study or administered into other brain areas. Alternatively, it could be the case that the SI test is a more sensitive measure for the effects of NPY in the BLA and had we injected a higher dose, we may have observed an effect on the EPM.…”

Section: Discussioncontrasting

confidence: 59%

Neuropeptide Y in the Amygdala Induces Long-Term Resilience to Stress-Induced Reductions in Social Responses But Not Hypothalamic–Adrenal–Pituitary Axis Activity or Hyperthermia

Sajdyk¹,

Johnson²,

Leitermann³

et al. 2008

J. Neurosci.

134

115

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Resilience to mental and physical stress is a key determinant for the survival and functioning of mammals. Although the importance of stress resilience has been recognized, the underlying neural mediators have not yet been identified. Neuropeptide Y (NPY) is a peptide known for its anti-anxiety-like effects mediated via the amygdala. The results of our current study demonstrate, for the first time that repeated administration of NPY directly into the basolateral nucleus of the amygdala (BLA) produces selective stress-resilient behavioral responses to an acute restraint challenge as measured in the social interaction test, but has no effect on hypothalamic-adrenal-pituitary axis activity or stress-induced hyperthermia. More importantly, the resilient behaviors observed in the NPY-treated animals were present for up to 8 weeks. Antagonizing the activity of calcineurin, a protein phosphatase involved in neuronal remodeling and present in NPY receptor containing neurons within the BLA, blocked the development of long-term, but not the acute increases in social interaction responses induced by NPY administration. This suggests that the NPY-induced long-term behavioral resilience to restraint stress may occur via mechanisms involving neuronal plasticity. These studies suggest one putative physiologic mechanism underlying stress resilience and could identify novel targets for development of therapies that can augment the ability to cope with stress.

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“…There is a significant correlation between CSF concentrations of NPY and ratings of social competence in schizophrenic patients [22]. Secondly, the behavior of npr-1 ( lf ) animals is motivated by avoidance of perceived aversive conditions, which is consistent with the role of NPY as an anxiolytic agent in rodents [23,24]. (3) Drugs used to treat schizophrenia reduce social feeding in C. elegans (via tranquilizing effects?).…”

Section: Social Withdrawal and Asociality Versus Social Feedingmentioning

confidence: 97%

Crossing the Worm-Brain Barrier by Using <b><i>Caenorhabditis elegans</i></b> to Explore Fundamentals of Human Psychiatric Illness

Dwyer¹

2017

Complex Psychiatry

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Endophenotypes and Research Domain Criteria (RDoC) represent recent efforts to deconvolute psychiatric illnesses into fundamental symptom clusters or biological markers more closely linked to genetic influences. By taking this one step farther, these biomarkers can be reduced to protophenotypes - endophenotypes conserved during evolution - with counterparts in lower organisms including Caenorhabditis elegans and Drosophila. Striking conservation in C. elegans of genes that increase the risk for mental illness bolsters the relevance of this model system for psychiatric research. Here, I review the characterization of several protophenotypes that are relevant for asociality, avolition/anhedonia, prepulse inhibition, and anorexia. Interestingly, the analogous behavioral defects in C. elegans are also corrected by psychotropic drugs used to treat the corresponding symptoms in man and/or are mediated by the same neurotransmitters. Overall, there is much we can learn about the complex human brain by studying simpler nervous systems directing evolutionarily conserved behaviors. The potential for generating important new insights from model organisms appears limitless when we begin to recognize the vestiges of evolution in ourselves.

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Anxiolytic-like effect of neuropeptide Y (NPY) and NPY13–36 microinjected into vicinity of locus coeruleus in rats

Cited by 91 publications

References 26 publications

Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

Neuropeptide Y in the Amygdala Induces Long-Term Resilience to Stress-Induced Reductions in Social Responses But Not Hypothalamic–Adrenal–Pituitary Axis Activity or Hyperthermia

Crossing the Worm-Brain Barrier by Using <b><i>Caenorhabditis elegans</i></b> to Explore Fundamentals of Human Psychiatric Illness

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