scholarly journals Antipruritic Effect of Nalbuphine, a Kappa Opioid Receptor Agonist, in Mice: A Pan Antipruritic

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5517
Author(s):  
Saadet Inan ◽  
Nae Dun ◽  
Alan Cowan
Keyword(s):  
Opioid Receptor ◽  
Skin Diseases ◽  
Kappa Opioid Receptor ◽  
Dependent Manner ◽  
Kappa Opioid ◽  
Knock Out ◽  
Chronic Itch ◽  
The Usa ◽  
Knock Out Mice ◽  
Hiv 1

Antipruritic effects of kappa opioid receptor (KOR) agonists have been shown in rodent models of acute and chronic scratching (itchlike behavior). Three KOR agonists, nalfurafine, difelikefalin, and nalbuphine, are in clinical studies for antipruritic effects in chronic itch of systemic and skin diseases. Nalfurafine (in Japan) and difelikefalin (in the USA) were approved to be used in the treatment of chronic itch in hemodialysis patients. The FDA-approved nalbuphine has been used in clinic for over 40 years, and it is the only narcotic agonist that is not scheduled. We aimed to study (a) antiscratch activity of nalbuphine against TAT-HIV-1 protein (controls HIV transcription)-, deoxycholic acid (DCA, bile acid)-, and chloroquine (CQ)-induced scratching in a mouse model of acute itch; and (b) whether the effect of nalbuphine is produced via KORs. First, dose–responses were developed for pruritogens. Mice were pretreated with nalbuphine (0.3–10 mg/kg) and then a submaximal dose of pruritogens were administered and the number of scratching bouts was counted. To study if the antiscratch effect of nalbuphine is produced via KOR, we used KOR knock out mice and pharmacologic inhibition of KORs using nor-binaltorphimine, a KOR antagonist. For this aim, we used CQ as a pruritogen. We found that: (a) TAT-HIV-1 protein elicits scratching in a dose-dependent manner; (b) nalbuphine inhibits scratching induced by TAT-HIV-1, DCA, and CQ dose-dependently; and (c) nalbuphine inhibits scratching induced by CQ through KORs. In conclusion, nalbuphine inhibits scratching elicited by multiple pruritogens.

scholarly journals ­­­­­The kappa opioid receptor agonist U50,488H did not affect brain-stimulation reward while it elicited conditioned place aversion in mice

2020 ◽  
Author(s):  
Peng Huang ◽  
Taylor Gentile ◽  
John Muschamp ◽  
Lee-Yuan Liu-Chen
Keyword(s):  
Opioid Receptor ◽  
Brain Stimulation ◽  
Kappa Opioid Receptor ◽  
Brain Stimulation Reward ◽  
Conditioned Place Aversion ◽  
Dependent Manner ◽  
Kappa Opioid ◽  
Two Phase ◽  
Place Aversion ◽  
Opioid Receptor Agonist

Abstract Objective: Selective kappa opioid receptor (KOR) agonists were shown to produce a dose-dependent depression of brain-stimulation reward (BSR) in the rat intracranial self-stimulation (ICSS) tests. However, limited studies using mice produced less conclusive results. Here the effects of U50,488H were re-examined on BSR in mice with a larger cohort of animals. Results: Forty C57BL/6J male mice were implanted with the electrodes in medial forebrain bundle. About a week after surgery, mice were subject to ICSS training. Only eighteen passed the two-phase procedures, at which point they readily spun the wheels to obtain reinforcing effect of BSR, and were used for the ICSS tests. Compared with saline (s.c.), U50,488H (2 mg/kg, s.c.) did not have effects on the BSR thresholds within 1 h post-treatment, while it decreased the maximum wheel-spinning rates in a time-dependent manner. In contrast, cocaine (5 mg/kg, s.c.) decreased the BSR thresholds time-dependently without affecting the maximum wheel-spinning rates in the same cohort of mice, demonstrating the validity of our mouse ICSS models. For comparison, U50,488H (2 mg/kg, s.c.) induced significant conditioned place aversion (CPA) in a different cohort of mice without surgeries. Thus, ICSS may not be an appropriate test for KOR agonist-induced aversion in mice.

scholarly journals ­­­­­The kappa opioid receptor agonist U50,488H did not affect brain-stimulation reward while it elicited conditioned place aversion in mice

2020 ◽  
Author(s):  
Peng Huang ◽  
Taylor Gentile ◽  
John Muschamp ◽  
Lee-Yuan Liu-Chen
Keyword(s):  
Opioid Receptor ◽  
Brain Stimulation ◽  
Kappa Opioid Receptor ◽  
Brain Stimulation Reward ◽  
Conditioned Place Aversion ◽  
Dependent Manner ◽  
Kappa Opioid ◽  
Two Phase ◽  
Place Aversion ◽  
Opioid Receptor Agonist

Abstract Objective: Selective kappa opioid receptor (KOR) agonists were shown to produce a dose-dependent depression of brain-stimulation reward (BSR) in the rat intracranial self-stimulation (ICSS) tests. However, limited studies using mice produced less conclusive results. Here the effects of U50,488H were re-examined on BSR in mice with a larger cohort of animals. Results: Forty C57BL/6J male mice were implanted with the electrodes in medial forebrain bundle. About a week after surgery, mice were subject to ICSS training. Only eighteen passed the two-phase procedures, at which point they readily spun the wheels to obtain reinforcing effect of BSR, and were used for the ICSS tests. Compared with saline (s.c.), U50,488H (2 mg/kg, s.c.) did not have effects on the BSR thresholds within 1 h post-treatment, while it decreased the maximum wheel-spinning rates in a time-dependent manner. In contrast, cocaine (5 mg/kg, s.c.) decreased the BSR thresholds time-dependently without affecting the maximum wheel-spinning rates in the same cohort of mice, demonstrating the validity of our mouse ICSS models. For comparison, U50,488H (2 mg/kg, s.c.) induced significant conditioned place aversion (CPA) in a different cohort of mice without surgeries. Thus, ICSS may not be an appropriate test for KOR agonist-induced aversion in mice.

scholarly journals Dysregulation of kappa-opioid receptor systems by chronic nicotine modulate the nicotine withdrawal syndrome in an age-dependent manner

2012 ◽  
Vol 224 (2) ◽  
pp. 289-301 ◽  
Author(s):  
Hugo A. Tejeda ◽  
Luis A. Natividad ◽  
James E. Orfila ◽  
Oscar V. Torres ◽  
Laura E. O’Dell
Keyword(s):  
Opioid Receptor ◽  
Withdrawal Syndrome ◽  
Nicotine Withdrawal ◽  
Kappa Opioid Receptor ◽  
Dependent Manner ◽  
Kappa Opioid ◽  
Chronic Nicotine ◽  
Age Dependent

scholarly journals ­­­­­The kappa opioid receptor agonist U50,488H did not affect brain-stimulation reward while it elicited conditioned place aversion in mice

2020 ◽  
Author(s):  
Peng Huang ◽  
Taylor Gentile ◽  
John Muschamp ◽  
Lee-Yuan Liu-Chen
Keyword(s):  
Opioid Receptor ◽  
Brain Stimulation ◽  
Kappa Opioid Receptor ◽  
Brain Stimulation Reward ◽  
Conditioned Place Aversion ◽  
Dependent Manner ◽  
Kappa Opioid ◽  
Two Phase ◽  
Place Aversion ◽  
Opioid Receptor Agonist

Abstract Objective Selective kappa opioid receptor (KOR) agonists were shown to produce a dose-dependent depression of brain-stimulation reward (BSR) in the rat intracranial self-stimulation (ICSS) tests. However, limited studies using mice produced less conclusive results. Here the effects of U50,488H were re-examined on BSR in mice with a larger cohort of animals. Results Forty C57BL/6J male mice were implanted with the electrodes in medial forebrain bundle. About a week after surgery, mice were subject to ICSS training. Only eighteen passed the two-phase procedures, at which point they readily spun the wheels to obtain reinforcing effect of BSR, and were used for the ICSS tests. Compared with saline (s.c.), U50,488H (2 mg/kg, s.c.) did not have effects on the BSR thresholds within 1 h post-treatment, while it decreased the maximum wheel-spinning rates in a time-dependent manner. In contrast, cocaine (5 mg/kg, s.c.) decreased the BSR thresholds time-dependently without affecting the maximum wheel-spinning rates in the same cohort of mice, demonstrating the validity of our mouse ICSS models. For comparison, U50,488H (2 mg/kg, s.c.) induced significant conditioned place aversion (CPA) in a different cohort of mice without surgeries. Thus, ICSS may not be an appropriate test for KOR agonist-induced aversion in mice.

New C(2)-sulfonyl ester-type Salvinorin A ligands to the kappa-opioid receptor

Planta Medica ◽  
2015 ◽  
Vol 81 (05) ◽  
Author(s):  
PR Polepally ◽  
A Keasling ◽  
K White ◽  
E Vardy ◽  
BL Roth ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Salvinorin A ◽  
Kappa Opioid

scholarly journals The Role of Dynorphin and the Kappa Opioid Receptor in Schizophrenia and Major Depressive Disorder: A Translational Approach

2020 ◽  
Author(s):  
Samuel David Clark
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Healthy Volunteers ◽  
Opioid Receptor ◽  
Clinical Data ◽  
Potential Role ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Major Depressive

AbstractThe kappa opioid receptor (KOR) and its endogenous ligands dynorphins (DYN) have been implicated in the development or symptomatology of a variety of neuropsychiatric disorders. This review covers a brief history of the development of KOR agonists and antagonists, their effects in healthy volunteers, and the potential role of DYN/KOR dysfunction in schizophrenia and major depressive disorder from a translational perspective. The potential role of DYN/KOR dysfunction in schizophrenia is based on several lines of evidence. Selective KOR agonists induce affective states in healthy volunteers with similarities to the symptoms of schizophrenia. Studies have shown increased DYN in patients with schizophrenia, although the data have been mixed. Finally, meta-analytic data have shown that opioid antagonists are associated with reductions in the symptoms of schizophrenia. The potential role of DYN/KOR dysfunction in major depressive disorder is also based on a combination of preclinical and clinical data. Selective KOR agonists have shown pro-depressive effects in human volunteers, while selective KOR antagonists have shown robust efficacy in several preclinical models of antidepressant activity. Small studies have shown that nonselective KOR antagonists may have efficacy in treatment-resistant depression. Additionally, recent clinical data have shown that the KOR may be an effective target for treating anhedonia, a finding relevant to both schizophrenia and depression. Finally, recommendations are provided for translating preclinical models for schizophrenia and major depressive disorder into the clinic.

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