TITLE:
Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait
AUTHORS:
Amanda L. Schott, Betty Zimmerberg
KEYWORDS:
Anxiety, Substance P, Neurokinin Receptor, Spantide, Ultrasonic Vocalizations
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.5 No.9,
August
7,
2014
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.