Anxiolytic-like effect of central administration of NOP receptor antagonist UFP-101 in rats submitted to the elevated T-maze

Duzzioni, Marcelo; Duarte, Filipe S.; Leme, Leandro Rinaldi; Gavioli, Elaine C.; Lima, Thereza Christina Monteiro de

doi:10.1016/j.bbr.2011.03.056

Cited by 26 publications

(14 citation statements)

References 52 publications

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“…Consistent with this idea, Ko and Naughton [24] have demonstrated that intrathecal administration of the endogenous NOP receptor ligand nociceptin/orphanin FQ (N/OFQ), unlike morphine, produced antinociceptive effects in monkeys without evidence of sedation. Alternatively, the greater effectiveness of SCH 221510 than morphine under the present conditions may reflect anxiolytic effects of NOP agonists that have been observed previously in rats [12; 15; 17; 18]. From this perspective, anxiolytic effects of the NOP receptor agonist may be viewed as countering the suppression of organized behavior by the nociceptive stimulus.…”

Section: Discussionmentioning

confidence: 61%

Operant nociception in nonhuman primates

Kangas

Bergman²

2014

Pain

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The effective management of pain is a longstanding public health concern. Morphine-like opioids have long been front-line analgesics, but produce undesirable side effects that can limit their application. Slow progress in the introduction of novel improved medications for pain management over the last 5 decades has prompted a call for innovative translational research, including new preclinical assays. Most current in vivo procedures (e.g., tail flick, hot plate, warm water tail withdrawal) assay the effects of nociceptive stimuli on simple spinal reflexes or unconditioned behavioral reactions. However, clinical treatment goals may include the restoration of previous behavioral activities, which can be limited by medication-related side-effects that are not measured in such procedures. The present studies describe an apparatus and procedure to study the disruptive effects of nociceptive stimuli on voluntary behavior in nonhuman primates, and the ability of drugs to restore such behavior through their analgesic actions. Squirrel monkeys were trained to pull a cylindrical thermode for access to a highly palatable food. Next, sessions were conducted in which the temperature of the thermode was increased stepwise until responding stopped, permitting the determination of stable nociceptive thresholds. Tests revealed that several opioid analgesics, but not d-amphetamine or Δ9-THC, produced dose-related increases in threshold that were antagonist-sensitive and efficacy-dependent, consistent with their effects using traditional measures of antinociception. Unlike traditional reflex-based measures, however, the results also permitted the concurrent evaluation of response disruption, providing an index with which to characterize the behavioral selectivity of antinociceptive drugs.

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Section: Discussionmentioning

confidence: 61%

Operant nociception in nonhuman primates

Kangas

Bergman²

2014

Pain

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“…For example, UFP-101 had anxiolytic-like effects after acute dosing in rats in an elevated T-maze (Duzzioni et al, 2011). Although anxiolytic-like effects of acute dosing of agonists has been reported (Table 4), there are exceptions that complicate general understanding of the N/OFQ system at this time.…”

Section: Stress Anxiety and Moodmentioning

confidence: 99%

The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence

Witkin

Statnick

Rorick-Kehn

et al. 2014

Pharmacology & Therapeutics

179

162

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Nociceptin/Orphanin FQ (N/OFQ) is a 17 amino acid peptide that was deorphanized in 1995. The generation of specific agonists, antagonists and receptor deficient mice and rats has enabled progress in elucidating the biological functions of nociceptin. In addition, radio-imaging technologies have been advanced for investigation of this system in animals and humans. Together with traditional neurobehavioral techniques, these tools have been utilized to identify the biological significance of the N/OFQ system and its interacting partners. The present commentary focuses on the role of N/OFQ in the regulation of feeding and body weight homeostasis, stress and the stress-related psychiatric disorders of depression and anxiety, and in drug and alcohol dependence. Critical evaluation of the current scientific preclinical literature suggests that small molecule modulators of nociceptin opioid peptide receptors (NOP) might be useful in the treatment of diseases related to these biological functions. In particular, the literature data suggest that antagonism of NOP receptors will produce anti-obesity and antidepressant activities in humans. However, there are also contradictory data discussed. The current literature on the role of N/OFQ in anxiety and addiction, on the other hand points primarily to a role of agonist modulation being potentially therapeutic. Some drug-like molecules that function either as agonists or antagonists of NOP receptors have been optimized for human clinical study to test some of these hypotheses. The discovery of PET ligands for NOP receptors, combined with the pharmacological tools and burgeoning preclinical data set discussed here bodes well for a rapid advancement of clinical understanding and potential therapeutic benefit.

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“…In fact, it has been shown that N/OFQ (0.01-3 nmol) and NOP agonists induce anxiolytic-like effects in mice in the elevated plus maze (Jenck et al 1997), hole-board (Kamei et al 2004), light-dark box (Jenck et al 1997;Gavioli and Calo' 2006), defense test battery (Griebel et al 1999), and defensive burying test (Vitale et al 2006). Regarding the ETM test, very few findings are still available; Duzzioni et al (2011) showed that icv N/OFQ (only one dose was tested-0.3 nmol) in rats did not affect anxiety-related behaviors. Microinjections of N/ OFQ (32 pmol), again tested at just one dose, in the central amygdala in rats did not change the latency to enter in an open arm in the ETM test (Uchiyama et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Nociceptin/orphanin FQ induces simultaneously anxiolytic and amnesic effects in the mouse elevated T-maze task

Asth

Correia

Lobão-Soares

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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Studies have shown a close relationship between anxiety and aversive memory processing, but few animal models are suitable for investigating the effects of a given compound on anxiety and memory simultaneously. A growing body of evidence suggests anxiolytic and amnesic effects of nociceptin/orphanin FQ (N/OFQ). The mouse elevated T-maze (ETM) has been shown to detect the effects of drugs on anxiety and memory at the same time. In this study, the effects of intracerebroventricular N/OFQ injected before or immediately after training session were assessed in the ETM task. When pretraining injected, N/OFQ 0.1 nmol significantly decreased the latency to enter an open arm in the training session compared to control, which is suggestive of anxiolysis. In addition, N/OFQ (0.1 and 1 nmol) significantly reduced the latency to enter an open arm during the test session compared to control, thus suggesting memory impairments. However, when N/OFQ was administered posttraining, it did not affect memory retrieval. No alterations in locomotion were detected in N/OFQ-treated mice in the open field test. In conclusion, these findings are discussed considering the simultaneous anxiolytic and amnesic effects of N/OFQ.

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Anxiolytic-like effect of central administration of NOP receptor antagonist UFP-101 in rats submitted to the elevated T-maze

Cited by 26 publications

References 52 publications

Operant nociception in nonhuman primates

Operant nociception in nonhuman primates

The biology of Nociceptin/Orphanin FQ (N/OFQ) related to obesity, stress, anxiety, mood, and drug dependence

Nociceptin/orphanin FQ induces simultaneously anxiolytic and amnesic effects in the mouse elevated T-maze task

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