Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait

Amanda L Schott,Betty Zimmerberg

doi:10.4236/pp.2014.59096

Abstract

Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.

Highlights

Anxiety disorders are among the most prevalent mental health disorders, including social phobia, post-traumatic stress disorder, obsessive-compulsive disorder, and panic disorder
This study examined the effects of an NK1 receptor antagonist, Spantide II, on ultrasonic vocalizations (USVs) rates in 7-day-old high and low line week-old pups following brief separation from the dam
This interaction is explained by the finding that the effect of condition was only significant in the high line subjects; no significant effects of the drug were apparent in low line subjects

Summary

Introduction

Anxiety disorders are among the most prevalent mental health disorders, including social phobia, post-traumatic stress disorder, obsessive-compulsive disorder, and panic disorder. Estimates of the prevalence of anxiety disorders range from 5.3% in African cultures to 10.4% in Euro/Anglo cultures [1]. Fear responses can be observed very early in life; for example, the normative response of separation anxiety appears in infants at around 18 months of age and can persist until about three years of age. The median age for disorder onset was earlier for anxiety disorders (6 years of age) than for other mental health illnesses. Anxiety disorders in childhood and adolescence are associated with a variety of negative outcomes, including psychosocial and school impairments and an increase in suicide risk [3]

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Conclusion