Participation of NK1 receptors of the amygdala on the processing of different types of fear

Highlights

• The role of SP/NK1 receptors of CeA and BLA was tested in distinct types of fear.

• In EPM test, SP intra-CeA evoked anxiogenic-like effects through NK1 receptors.

• SP is not tonically active since NK1-blockade had no effect on behavior in EPM.

• In intense fear intra-CeA NK1-blockade reduced the time of dPAG-PSF.

• NK1 receptors of distinct nuclei act differently on defensive reactions of fear.

Abstract

The amygdala, medial hypothalamus, dorsal periaqueductal gray (dPAG), superior and inferior colliculus together constitutes the encephalic aversion system which has been considered the main neural substrate for the integration of unconditioned aversive behavioral states. Within the amygdala the basolateral nucleus (BLA) is thought to act as a filter for innate and learned aversive information to higher structures, whereas the central nucleus (CeA) is considered the main output for the expression of fear reactions through projections to limbic and brainstem regions. Although neurokinin (NK) receptors are abundant in the amygdala, their role in the processing and expression of fear is yet unclear. In this study, we examined the role of SP/NK1 receptor system of the CeA and BLA on the expression of defensive responses elaborated by Wistar rats submitted to elevated plus maze (EPM) and to electrical stimulation (ES) of the dPAG. For EPM test, cannulae were implanted in the CeA and BLA for injections of substance P (SP – 10 and 100 pmol/0.2 μL) and spantide (SPA – 10, 100 and 500 pmol/0.2 μL). For ES of dPAG, aversive thresholds for freezing and escape responses as well as post-stimulation freezing (PSF) were measured in rats treated with PBS and SPA (100 pmol/0.2 μL) in CeA. Injections of SP into the CeA, but not the BLA, produced anxiogenic-like effects in the EPM test. SPA injected into the CeA had no effect on the exploratory behavior of rats submitted to the EPM but blocked the effects of SP. The duration of dPAG-PSF was also reduced significantly following injection of SPA in CeA but had no effect on thresholds for freezing and escape responses. The EPM gives the animal a control over its environment i.e. the option to choose or not to enter into the open arm and dPAG-PSF is thought to reflect a period when the animal evaluates the significance of dPAG-evoked aversion once the unconditioned responses of freezing and escape were elicited. The data indicate that SP may be involved in mediating responses of the animal in only certain types of aversive behavior and suggests a differential participation of the NK1 receptors in the processing of distinct types of fear in the amygdala.