Differential effects of neurokinin-1 receptor activation in subregions of the periaqueductal gray matter on conditional and unconditional fear behaviors in rats.

Abstract

Central neurokinin-1 (NK-1) receptors are thought to modulate aversion, whereas the periaqueductal gray matter (PAG) is a common pathway for the integration of fear behaviors. The authors determined whether injection of an NK-1 agonist (GR73632) into subregions of the PAG would alter fear-related behaviors. Behavioral inactivity was increased by GR73632 injected into the caudodorsal PAG or the dorsal raphe. Flight behavior induced by stimulation of the dorsal PAG or by a footshock was decreased after injection of GR73632 into the dorsal PAG. Rats that had 6 pairings of a tone with a footshock after injection of GR73632 into the dorsal PAG displayed more freezing behavior than controls at the beginning of the session. However, there was no change in the shock- or the tone-induced freezing because some GR73632-treated rats, but no controls, froze during the baseline period. It is concluded that NK-1 receptors in the dorsal PAG modulate the unconditional but not the mnemonic aspects of fear behaviors.

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

“…A role for the PAG in mediating fear and anxiety has also been well documented (Bandler and Shipley, 1994;Blanchard et al, 1981;DeOca et al, 1998) and SP neurotransmission has been implicated here as well (De Araujo et al, 1999;Gregg and Siegel, 2003;Mongeau et al, 1998). The findings of our study support a critical role of SP neurotransmission within the PAG in fear-potentiated startle and indicate more specifically that these effects may be mediated primarily by SP receptors in the rostral dlPAG.…”

Functional magnetic resonance mapping of intracerebroventricular infusion of a neuroactive peptide in the anaesthetised rat

“…Similar behavioural and cardiovascular changes were observed following focal cerebral administration of GR-73632 in rats (Elliott et al, 1991;Mongeau et al, 1998). Administration of GR-73632 (4.2 pmol/rat) in the lateral ventricle produced a rapid onset and sustained rCBV response showing signal increases in the cortex and sub-cortical structures such as the caudate putamen, the ventral tegmental area, the lateral hypothalamic nucleus, and the amygdala.…”

Evidence for mediation of nociception by injection of the NK-3 receptor agonist, senktide, into the dorsal periaqueductal gray of rats

“…NK-1-mediated mechanisms have been associated with anxiety-like behavior in several animal species (Ebner and Singewald 2006;Dableh et al 2005;Kramer et al 1998;Varty et al 2002;Duarte et al 2004). The anxiogenic-like effects of substance P in the dPAG may be mediated by NK-1 receptors (Mongeau et al 1998;De Araújo et al 2001b;Duarte et al 2004;Bassi et al 2007a, b).…”

“…Injections of a C-terminal fragment of substance P also induce behavioral activation with defensive characteristics (De Araújo et al 1999, 2001b. The anxiogenic-like effects of substance P in the dPAG appear to be mediated by NK-1 receptors (Mongeau et al 1998;De Araújo et al 2001b;Duarte et al 2004;Bassi et al 2007b). The observation that NK-1 receptor antagonists may be effective in the treatment of depression in patients with symptoms of appreciable anxiety has led to research efforts aimed at the development of therapies for both depression and anxiety (Kramer et al 1998;Santarelli et al 2001;Ranga and Krishnan 2002;Quartara and Altamura 2006).…”