LAUSR

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. HIGHLIGHTSSubstance P microinjections in the CeA and MeA but not BLA elicit anxiety‐like behavior.Substance P exerts antinociceptive effects only when microinjected in the MeA.Substance P microinjections did not elicit USVs.NK‐1 receptors only in the CeA are involved in the production of anxiety‐like behavior.NK‐1 receptors in the MeA are responsible for the antinociceptive effects of substance P.