Restraint Stress Alters Nociceptin/Orphanin FQ and CRF Systems in the Rat Central Amygdala: Significance for Anxiety-Like Behaviors

Abstract

Corticotropin releasing factor (CRF) is the primary mediator of stress responses, and nociceptin/orphanin FQ (N/OFQ) plays an important role in the modulation of these stress responses. Thus, in this multidisciplinary study, we explored the relationship between the N/OFQ and the CRF systems in response to stress. Using in situ hybridization (ISH), we assessed the effect of body restraint stress on the gene expression of CRF and N/OFQ-related genes in various subdivisions of the amygdala, a critical brain structure involved in the modulation of stress response and anxiety-like behaviors. We found a selective upregulation of the NOP and downregulation of the CRF 1 receptor transcripts in the CeA and in the BLA after body restraint. Thus, we performed intracellular electrophysiological recordings of GABA A -mediated IPSPs in the central nucleus of the amygdala (CeA) to explore functional interactions between CRF and N/OFQ systems in this brain region. Acute application of CRF significantly increased IPSPs in the CeA, and this enhancement was blocked by N/OFQ. Importantly, in stress-restraint rats, baseline CeA GABAergic responses were elevated and N/OFQ exerted a larger inhibition of IPSPs compared with unrestraint rats. The NOP antagonist [Nphe1]-nociceptin(1-13)NH2 increased the IPSP amplitudes in restraint rats but not in unrestraint rats, suggesting a functional recruitment of the N/OFQ system after acute stress. Finally, we evaluated the anxiety-like response in rats subjected to restraint stress and nonrestraint rats after N/OFQ microinjection into the CeA. Intra-CeA injections of N/OFQ significantly and selectively reduced anxiety-like behavior in restraint rats in the elevated plus maze. These combined results demonstrate that acute stress increases N/OFQ systems in the CeA and that N/OFQ has antistress properties.

Neuropeptide S differently modulates alcohol-related behaviors in alcohol-preferring and non-preferring rats

“…These rats showed that NPS specifically exerts anxiolytic effects on msP rats. A similar phenomenon was previously observed for drugs such as nociception agonists and CRF1 receptor antagonists; both classes of compounds possess marked anxiolytic effects and reduced alcohol drinking in msP rats but not in heterogeneous Wistar rats (Ayanwuyi et al 2013; Ciccocioppo et al 2014; de Guglielmo et al 2015; Gehlert et al 2007). Most importantly, our finding agrees with previous studies published in genetically selected alcohol-preferring P rats, in which ICV administration of NPS attenuated home cage alcohol drinking and elicited a marked anxiolytic effect (Badia-Elder et al 2008).…”

Stress and opioids: Role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference

“…Furthermore, acute and chronic stress induces differential changes in the ppNN/OFQ expression, with their decreased expression in the central amygdala in response to acute stressor and increased expression in the bed nucleus and reticular thalamus in response to a repeated restraint stressor (Delaney et al, 2012). Injection of N/OFQ in the central nucleus of amygdala is shown to significantly and selectively reduce anxiety-like behavior (in the elevated plus maze test) in restraint rats, suggesting that acute stress activates the N/OFQ system in this brain region to produce anti-stress effects (Ciccocioppo et al, 2014). In response to acute restraint stress, the enhanced expression of N/OFQ in the CA1, CA3, and dentate gyrus of the hippocampus and rise in the plasma corticosterone levels has been documented.…”

Angiotensin type 1a receptors on corticotropin‐releasing factor neurons contribute to the expression of conditioned fear1

“…Furthermore, because AT 1a R and CRF are both expressed in moderate levels in the CeA (Ciccocioppo et al, 2014, Shekhar et al, 2005, Von Bohlen Und Halbach and Albrecht, 1998b) and PVN (Premer et al, 2013, Aguilera et al, 1995a), we expected that this knockout would be pronounced in these areas.…”