Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats

Chang, Ho‐Wan; Saito, Tsuyoshi; Ohiwa, Nao; Tateoka, Masaru; Deocaris, Custer C.; Fujikawa, Takahiko; Soya, Hideaki

doi:10.1016/j.neures.2006.11.009

Cited by 61 publications

(53 citation statements)

References 24 publications

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“…In contrast to the hyperarousal response, OX1R blockade did not affect the cage-exchange stressinduced ACTH release in mice, suggesting that OX1Rs are not directly involved in HPA axis activation elicited by this Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal psychological stress model. A putative OX2R-mediated effect might be rather expected since increase in ACTH levels by swimming stress was attenuated with prior central infusion of an OX2R antagonist (Chang et al, 2007), a result consistent with the predominance of OX2R in the PVN (Marcus et al, 2001). However, in a later study, administration of the dual OX1/2R antagonist almorexant in rats failed to alter the release of corticosterone in basal and various stress conditions (novelty, social stress, and restraint stress) or the release of ACTH upon pharmacological challenge with corticotrophinreleasing factor (Steiner et al, 2013b).…”

Section: Discussionmentioning

confidence: 99%

A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

Bonaventure

Yun

Johnson

et al. 2015

J Pharmacol Exp Ther

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Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, Although compound 56 did not alter spontaneous sleep in rats and in wildtype mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate-induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states.

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Section: Discussionmentioning

confidence: 99%

A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

Bonaventure

Yun

Johnson

et al. 2015

J Pharmacol Exp Ther

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“…Functional consideration of an orexin-PVT emotional arousal system It is well documented that orexins can produce a stress-like response by enhancing the activity of the hypothalamicpituitary-adrenal axis and the secretion of stress hormones in the circulation (Chang et al 2007;Ida et al 2000;Jaszberenyi et al 2000;Kuru 2000;Sakamoto et al 2004;Samson et al 2002Samson et al , 2007. In turn, orexin neurons may be activated by novelty-stress, pain, and contextual cues associated with shock (Espana et al 2003;Furlong et al 2009;Watanabe et al 2005;Winsky-Sommerer et al 2004;Zhu et al 2002), but not other stressors like exposure to cold and restraint (Furlong et al 2009;Kiss 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The antagonist SB334867 has a 50-fold selectivity for OX1R compared to OX2R whereas TCSOX229 has a 250-fold selectivity for the OX2R over the OX1R (Duxon et al 2001;Hirose et al 2003). Similar doses of orexin antagonists were effective at blocking some of the behavioral effects of orexins (Chang et al 2007;Hollander et al 2008). …”

Section: Ethological Behavior Analysismentioning

confidence: 99%

Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats

et al. 2010

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“…On the other hand, systemic injections of SB 334867, at doses that significantly decreased high-fat food self-administration, had no effect on reinstatement induced by pellet-priming, yohimbine or hypocretin 1. These data potentially suggest that the role of hypocretin 1 in relapse to food seeking is mediated by Hcrt 2 receptors, an issue that can be explored pending the availability of selective Hcrt 2 receptor antagonists (Chang et al, 2007) or mixed Hcrt 1/ Hcrt 2 receptor antagonists (Brisbare-Roch et al, 2007). One possible explanation for the lack of effect of SB 334867 on reinstatement of food seeking is due to lower baseline response rates during tests for reinstatement versus selfadministration.…”

Section: Role Of Hcrt 1 Receptors In Food Self-administrationmentioning

confidence: 99%

Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high-fat food self-administration and reinstatement of food seeking in rats

2008

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Background and purpose:Many studies have demonstrated a role of hypocretin 1 (orexin 1) receptors in home-cage food consumption in rodents. However, the role of these receptors in operant food self-administration or relapse to food seeking in animal models is unknown. Experimental approach: In Experiment 1, we trained food-restricted rats (16-20 g per day) to lever press for high-fat (35%) pellets (3-6 h per day, every other day). We then tested the effect of the hypocretin 1 receptor antagonist SB 334867 (10, 20 mg kg À1 , i.p) on pellet self-administration. In Experiment 2, we trained rats to self-administer the food pellets, and following extinction of the food-reinforced responding, we tested the effect of hypocretin 1 (3 and 6 mg, i.c.v) on reinstatement of foodseeking and the effect of SB 334867 on this reinstatement. In Experiment 3, we tested the effect of SB 334867 on reinstatement induced by non-contingent pellet exposure (pellet-priming) or the pharmacological stressor yohimbine (2 mg kg À1 , i.p). Key results: SB 334867 attenuated high-fat pellet self-administration. In contrast, SB 334867 had no effect on reinstatement of lever presses induced by hypocretin 1, pellet-priming or yohimbine. Conclusions and implications: These data indicate that during dieting, hypocretin 1 receptors contribute to operant high-fat pellet self-administration, but not to relapse to food seeking induced by acute re-exposure to the food itself or by the induction of a stress-like state.

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Inhibitory effects of an orexin-2 receptor antagonist on orexin A- and stress-induced ACTH responses in conscious rats

Cited by 61 publications

References 24 publications

A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats

Differential effects of the hypocretin 1 receptor antagonist SB 334867 on high-fat food self-administration and reinstatement of food seeking in rats

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