Central NPY receptor-mediated alteration of heart rate dynamics in mice during expression of fear conditioned to an auditory cue

• Published in: Regulatory peptides Vol. 120; no. 1; pp. 205 - 214
• Main Authors: Tovote, Philip, Meyer, Michael, Beck-Sickinger, Annette G, von Hörsten, Stephan, Ove Ögren, Sven, Spiess, Joachim, Stiedl, Oliver
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15-08-2004; Amsterdam Elsevier
• Subjects: Animals; Arginine - analogs & derivatives; Arginine - pharmacology; Auditory fear conditioning; Auditory Perception - physiology; Autonomic nervous system; Biological and medical sciences; Bradycardia - metabolism; Bradycardia - pathology; Conditioning (Psychology); Cues; Fear - physiology; Fundamental and applied biological sciences. Psychology; Heart Rate - drug effects; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred C57BL; Neuropeptide Y; Neuropeptide Y - pharmacology; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Receptors, Neuropeptide Y - agonists; Receptors, Neuropeptide Y - antagonists & inhibitors; Receptors, Neuropeptide Y - metabolism; Stress; Swine; Telemetry; Vertebrates: endocrinology; Vertebrates: nervous system and sense organs; Neuropeptide Y; Auditory fear conditioning; Telemetry; Autonomic nervous system; Stress; Rodentia; Alteration; Heart rate; Vertebrata; Mammalia; Mouse; Dynamics; Animal; Conditioning; Biological receptor
• ISSN: 0167-0115; 1873-1686
• DOI: 10.1016/j.regpep.2004.03.011

Neuropeptide Y (NPY) is involved in the regulation of emotionality including fear and anxiety, which modulate autonomic control of cardiovascular function. We therefore investigated the central effects of porcine NPY, selective Y
1, Y
2 and Y
5 receptor agonists and a Y
1 receptor antagonist on heart rate (HR) and HR variability in freely moving mice using auditory fear conditioning. Intracerebroventricular (i.c.v.) injections were applied 15 min before the tone-dependent memory test. NPY dose-dependently induced bradycardia associated with decreased HR variability, and blunted the stress-induced tachycardic response. The selective Y
1 receptor antagonist BIBO 3304 blocked the NPY- and Y
1-receptor agonist-induced suppression of conditioned tachycardia without affecting basal HR. The tachycardia elicited by both conditioned and unconditioned stressor was effectively attenuated by the Y
1 receptor agonist. These results suggest a specific contribution of Y
1, but not Y
2 and Y
5 receptors, to modulation of emotional responses most likely unrelated to impairment or modulation of memory. The NPY-induced bradycardia is attributed to not yet characterized NPY receptor subtypes other than Y
1, Y
2 and Y
5, or a complex receptor interaction. In conclusion, NPY mediates central inhibition of sympathetic outflow, potentially coupled with attenuation of parasympathetic tone, i.e., mechanisms that may be associated with the reported anxiolytic action.