Roles of the bed nucleus of stria terminalis and of the amygdala in N/OFQ-mediated anxiety and HPA axis activation

Green, Megan K.; Barbieri, Emily V.; Brown, Brandon M.; Chen, Kir-Wei; Devine, Darragh P.

doi:10.1016/j.npep.2007.09.002

Cited by 47 publications

(45 citation statements)

References 34 publications

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“…Finally, the OFQ/N knockout mice did not adapt to repeated swim stress. However, the (Fernandez et al, 2004) and rats (Green et al, 2007) in the elevated plus-maze, open field, and light-dark box models. The present experiments with SCH 221510 are consistent, however, with previous findings with both OFQ/N (Jenck et al, 1997;Griebel et al, 1999) and the nonpeptide agonist Ro64-6198 (Jenck et al, 2000;Varty et al, 2005) that demonstrated robust anxiolytic-like profiles in multiple species and across a larger number of behavioral models.…”

Section: Discussionmentioning

confidence: 97%

The Anxiolytic-Like Effects of the Novel, Orally Active Nociceptin Opioid Receptor Agonist 8-[bis(2-Methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)

Varty¹,

Lu²,

Morgan³

et al. 2008

J Pharmacol Exp Ther

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Orphanin FQ/nociceptin (OFQ/N) is the endogenously occurring peptide ligand for the nociceptin opioid receptor (NOP) that produces anxiolytic-like effects in mice and rats. The present study assessed the anxiolytic-like activity of 8-[bis(2-methylphenyl)-methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510), a novel potent piperidine NOP agonist (EC 50 ϭ 12 nM) that binds with high affinity (K i ϭ 0.3 nM) and functional selectivity (Ͼ50-fold over the -, -, and ␦-opioid receptors). The anxiolytic-like activity and side-effect profile of SCH 221510 were assessed in a variety of models and the benzodiazepine, chlordiazepoxide (CDP), was included for comparison. The effects of chronic dosing of SCH 221510 were also assessed. Furthermore, the specificity of the anxiolytic-like effect of SCH 221510 was investigated with the NOP receptor antagonist 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) and the opioid receptor antagonist naltrexone. Like CDP (1-30 mg/kg i.p.), SCH 221510 (1-30 mg/kg p.o.) produced anxiolytic-like effects in the elevated plus-maze (rat and gerbil), Vogel conflict (rat), conditioned lick suppression (rat), fear-potentiated startle (rat), and pup separation-induced vocalization (guinea pig) assays. In the Vogel conflict, the anxiolytic-like effect of SCH 221510 (10 mg/kg) was attenuated by J-113397 (3-10 mg/kg p.o.), but not naltrexone (3-30 mg/kg i.p.). Additionally, the anxiolytic-like effects of SCH 221510 did not change appreciably following 14-day b.i.d. dosing in rats (10 mg/kg). Furthermore, unlike CDP, SCH 221510 (3-30 mg/kg) produced anxiolytic-like activity at doses that did not disrupt overt behavior. Collectively, these data suggest that NOP agonists such as SCH 221510 may have an anxiolytic-like profile similar to benzodiazepines, with a reduced side-effect liability.The nociceptin opioid receptor (NOP) was identified using a human cDNA library on the basis of close homology with the -, -, and ␦-opioid receptors (Bunzow et al., 1994;Mollereau et al., 1994). Subsequently, the endogenous ligand for the NOP receptor, orphanin FQ/nociceptin (OFQ/N), was identified from brain extracts and found to bind with high affinity to the NOP site, but not to -, -, or ␦-opioid receptors (Meunier et al., 1995;Reinscheid et al., 1995). Immunohistochemical studies demonstrated that the mRNA for OFQ/N and its precursor prepronociceptin, as well as immunoreactivity for the NOP receptor, are localized to corticolimbic regions of the central nervous system (CNS). These regions include the amygdaloid complex, septohippocampal regions, periaqueductal gray, locus coeruleus, and dorsal raphe nucleus (Darland et al., 1998). In vitro electrophysiological studies using brain slices have shown that OFQ/N has potent Article, publication date, and citation information can be found at

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Section: Discussionmentioning

confidence: 97%

The Anxiolytic-Like Effects of the Novel, Orally Active Nociceptin Opioid Receptor Agonist 8-[bis(2-Methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)

Varty¹,

Lu²,

Morgan³

et al. 2008

J Pharmacol Exp Ther

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“…Then, the rat was placed in open-field box individually during the 5-min period and recorded total distance moved and time of motor activity by tracking system [30]. The rats were freely moving in open field.…”

Section: Apparatusmentioning

confidence: 99%

The Effect of Severe Zinc Deficiency and Zinc Supplement on Spatial Learning and Memory

Boroujeni

Naghdi

Shahbazi

et al. 2009

Biol Trace Elem Res

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Zinc deficiency during pregnancy and during lactation has been shown to impair cognitive function and motor activity in offspring rats. In the present study, the effect of zinc deficiency and zinc supplement on spatial learning and memory in Morris Water Maze (MWM) and motor activity in open field were investigated. Pregnant rats after mating were divided to three groups. Control group fed a standard diet and a zinc deficient (ZnD) group fed a diet deficient in zinc (0.5-1.5 ppm) and a zinc supplement (ZnS) group fed a standard diet and enhanced zinc in the drinking water (10 ppm). All the diets were exposed during the last trisemester of pregnancy and during lactation. Rat's offspring in these groups were tested for spatial learning and memory in MWM at post natal day (PND) 56 and were tested for motor activity in open field at PND 66.The Escape Latency (EL) and Traveled Distance (TD) in the ZnD group were increased but Percentage of Time Spent in the target quadrant (PTS) was decreased compared to the control group. In addition, these were no significant differences in EL and TD, but PTS had significant increase in ZnS compared to the control group. In the open field, Total Distance Moved (TDM) and Time of Motor Activity (TMA) for the ZnD were decreased compared to the control group, but there were no significant differences in TDM and TMA between control and ZnS groups. These findings suggest that zinc deficiency during the last trimester of pregnancy and during lactation impaired spatial learning and memory in their offsprings and has also negative effect on motor activity. In addition, ZnS has a significant effect on spatial learning and memory but no effect on motor activity in their offsprings.

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“…In addition to its role in emotional behaviors, the BNST also regulates hypothalamic-pituitary-adrenal (HPA) activity (Cullinan et al 1993;Gray et al 1993;Herman et al 1994;Herman and Cullinan 1997;Sullivan et al 2004;Choi et al 2007Choi et al , 2008aGreen et al 2007). Because intra-BNST CGRP infusions increase fos immunoreactivity in the paraventricular nucleus of the hypothalamus (Sink et al 2011)-a nodal point in the HPA axis-and because HPA activity can influence fear learning and expression (Roozendaal 2002;Aerni et al 2004;Donley et al 2005;Schelling et al 2006;Soravia et al 2006;Tronel and Alberini 2007;Taubenfeld et al 2009;Jovanovic et al 2011;Zohar et al 2011;Atsak et al 2012;de Oliveira et al 2013), we also examined the contribution of BNST CGRP receptors to shockinduced corticosterone release.…”

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confidence: 99%

CGRP antagonist infused into the bed nucleus of the stria terminalis impairs the acquisition and expression of context but not discretely cued fear

2013

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Calcitonin gene-related peptide (CGRP) infusions into the bed nucleus of the stria terminalis (BNST) evoke increases in startle amplitude and increases in anxiety-like behavior in the plus maze. Conversely, intra-BNST infusions of the CGRP antagonist CGRP 8 -37 block unconditioned startle increases produced by fox odor. Here we evaluate the contribution of CGRP signaling in the BNST to the development and expression of learned fear. Rats received five pairings of a 3.7-sec light and footshock and were tested for fear-potentiated startle one or more days later. Neither pre-training (Experiment 1) nor pre-test (Experiment 2) infusions of the CGRP antagonist CGRP 8 -37 (800 ng/BNST) disrupted fear-potentiated startle to the 3.7-sec visual cue. However, in both experiments, CGRP 8 -37 infusions disrupted baseline startle increases that occurred when rats were tested in the same context as that in which they previously received footshock (Experiment 3). Intra-BNST CGRP 8 -37 infusions did not disrupt shock-evoked corticosterone release (Experiment 4). These data confirm previous findings implicating BNST CGRP receptors in fear and anxiety. They extend those results by showing an important contribution to learned fear and, specifically, to fear evoked by a shock-associated context rather than a discrete cue. This pattern is consistent with previous models of BNST function that have posited a preferential role in sustained anxiety as opposed to phasic fear responses. More generally, the results add to a growing body of evidence indicating behaviorally, possibly clinically, relevant modulation of BNST function by neuroactive peptides.

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Roles of the bed nucleus of stria terminalis and of the amygdala in N/OFQ-mediated anxiety and HPA axis activation

Cited by 47 publications

References 34 publications

The Anxiolytic-Like Effects of the Novel, Orally Active Nociceptin Opioid Receptor Agonist 8-[bis(2-Methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)

The Anxiolytic-Like Effects of the Novel, Orally Active Nociceptin Opioid Receptor Agonist 8-[bis(2-Methylphenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol (SCH 221510)

The Effect of Severe Zinc Deficiency and Zinc Supplement on Spatial Learning and Memory

CGRP antagonist infused into the bed nucleus of the stria terminalis impairs the acquisition and expression of context but not discretely cued fear

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