Inhibition of substance P-induced defensive behavior via neurokinin-1 receptor antagonism in the central and medial but not basolateral nuclei of the amygdala in male Wistar rats

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jul 3:77:146-154. doi: 10.1016/j.pnpbp.2017.03.026. Epub 2017 Apr 6.

Abstract

Rationale: The production of unconditioned defensive behaviors has been related to the amygdala, a key component of the encephalic aversion system. Microinjection of the neuropeptide substance P (SP) in the amygdala elicits defensive behaviors via the activation of type 1 neurokinin (NK-1) receptors. However, no studies have investigated whether intra-amygdala SP/NK-1 mechanisms can elicit other types of defensive responses, such as antinociception and ultrasonic vocalizations (USVs).

Methods: The present study investigated the effects of SP-induced activation of the neurokininergic system in three main nuclei of the amygdala-basolateral (BLA), central (CeA), and medial (MeA) nuclei-in rats that were subjected to the elevated plus maze (EPM), tail-flick test, and USV recording. The effects of SP in these amygdaloid nuclei were challenged with combined injections of the NK-1 receptor antagonist spantide.

Results: The present study showed that SP injections in the CeA and MeA but not BLA exerted anxiogenic-like effects. In contrast to the CeA, the anxiogenic-like effects of SP in the MeA were not dependent on NK-1 mechanisms. In the tail-flick test, SP microinjections produced antinociceptive effects only in the MeA through NK-1 receptor activation. No USV emissions were detected after the SP microinjections.

Conclusions: The present study showed that NK-1 receptors in the CeA and MeA but not BLA are involved in defensive reactions to conditions of fear. The present results may provide a better understanding of the neurochemical mediation of fear states.

Keywords: Amygdala; Elevated plus maze; Neurokinin; Rat; Tail-flick; Ultrasonic vocalizations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / drug effects*
  • Analgesics / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Fear / drug effects*
  • Fear / psychology*
  • Male
  • Maze Learning / drug effects
  • Microinjections
  • Neurokinin-1 Receptor Antagonists / pharmacology*
  • Rats
  • Receptors, Neurokinin-1 / metabolism*
  • Substance P / administration & dosage
  • Substance P / analogs & derivatives
  • Substance P / antagonists & inhibitors*
  • Substance P / pharmacology*
  • Vocalization, Animal / drug effects

Substances

  • Analgesics
  • Neurokinin-1 Receptor Antagonists
  • Receptors, Neurokinin-1
  • Substance P
  • spantide