Kappa opioid antagonist effects of the novel kappa antagonist 5?-guanidinonaltrindole (GNTI) in an assay of schedule-controlled behavior in rhesus monkeys

2002 ◽  
Vol 163 (3-4) ◽  
pp. 412-419 ◽  
Author(s):  
Stevens S. Negus ◽  
Nancy K. Mello ◽  
David C. Linsenmayer ◽  
R. Jones ◽  
Philip S. Portoghese
Keyword(s):  
Rhesus Monkeys ◽  
Opioid Antagonist ◽  
The Novel ◽  
Kappa Opioid

Antidepressant-Like Effects of the Novel Kappa Opioid Antagonist MCL-144B in the Forced-Swim Test

Pharmacology ◽  
2008 ◽  
Vol 81 (3) ◽  
pp. 229-235 ◽  
Author(s):  
J.D. Reindl ◽  
K. Rowan ◽  
A.N. Carey ◽  
X. Peng ◽  
J.L. Neumeyer ◽  
...  
Keyword(s):  
Forced Swim Test ◽  
Opioid Antagonist ◽  
The Novel ◽  
Kappa Opioid ◽  
Swim Test ◽  
Forced Swim

kappa-Opioid agonist inhibition of osmotically induced AVP release: preferential action at hypothalamic sites

1996 ◽  
Vol 270 (2) ◽  
pp. E367-E372 ◽  
Author(s):  
N. F. Rossi ◽  
D. P. Brooks
Keyword(s):  
Potent Inhibitor ◽  
Opiate Receptors ◽  
Opioid Antagonist ◽  
Posterior Pituitary ◽  
Opioid Agonist ◽  
Kappa Opioid ◽  
Water Diuresis ◽  
Kappa Agonist ◽  
Opioid Agonists ◽  
Kappa Opioid Agonist

Although several studies indicate that kappa-opioid agonists induce a water diuresis by inhibiting vasopressin (AVP) secretion, the locus of the kappa-receptors (neurohypophysial vs. hypothalamic) responsible for this effect remains unclear. We have ascertained the effect of the selective kappa-agonist BRL-52656 (BRL) on AVP secretion by using compartmentalized rat hypothalamoneurohypophysial explants in culture. When applied to the hypothalamus, nanomolar concentrations of BRL inhibited osmotically stimulated AVP secretion. This response was blocked by the highly selective kappa-opioid antagonist nor-binaltorphimine (BNI). However, osmotically stimulated AVP release was suppressed at the neurohypophysial site only by 100 nM BRL and was not reversed by BNI but only by naloxone. This dose of BRL, administered to the posterior pituitary compartment, did not appear to act by the agonist gaining access to hypothalamic kappa-opiate receptors, because BNI added to the hypothalamus failed to prevent the inhibition of AVP secretion. The data demonstrate that BRL is a potent inhibitor of osmotically stimulated AVP secretion via activation of kappa-opiate receptors within the hypothalamus, but that higher concentrations of the drug may also stimulate non-kappa-neurohypophysial opiate receptors that suppress AVP release.

scholarly journals Synergistic antidepressant-like effects between a kappa opioid antagonist (LY2444296) and a delta opioid agonist (ADL5859) in the mouse forced swim test

2016 ◽  
Vol 781 ◽  
pp. 53-59 ◽  
Author(s):  
Peng Huang ◽  
Julia Tunis ◽  
Christopher Parry ◽  
Ronald Tallarida ◽  
Lee-Yuan. Liu-Chen
Keyword(s):  
Forced Swim Test ◽  
Opioid Antagonist ◽  
Opioid Agonist ◽  
Kappa Opioid ◽  
Swim Test ◽  
Forced Swim

scholarly journals The effect of novel kappa opioid peptide receptor agonists on learning and memory in rats

2021 ◽  
Author(s):  
◽  
Susan Adele Welsh
Keyword(s):  
Recognition Memory ◽  
Side Effect ◽  
Memory Impairment ◽  
Perirhinal Cortex ◽  
Opioid Peptide ◽  
Salvinorin A ◽  
The Novel ◽  
Kappa Opioid ◽  
The Brain

<p>Kappa opioid peptide receptors (KOPrs) are a class of opioid receptors which shown analgesic and anti-addictive properties. Nonaddictive analgesics would be beneficial as morphine, one of the most commonly prescribed opioids for chronic pain, activates the brain reward system and can lead to addiction. Although medical research is progressing rapidly, there is still no treatment for psychostimulant abuse. KOPr agonists show promise in this regard but display undesirable side effects and could negatively affect memory. Salvinorin A (Sal A), a structurally unusual KOPr agonist, has a reduced side effect profile compared to the more traditional KOPr agonists such as U50,488. The effect of Sal A and U50,488 on memory is controversial as they have both been shown to induce a memory impairment and also to improve memory impairments. Sal A also has a poor pharmacokinetic profile with a short duration of action. Structural analogues of Sal A have improved pharmacokinetic and side effect profiles compared to Sal A yet retain the analgesic and anti-addiction properties. This thesis will investigate whether Sal A analogues, namely Ethynyl Sal A (Ethy Sal A), Mesyl Salvinorin B (Mesyl Sal B), and Bromo Salvinorin A (Bromo Sal A), produce a memory impairment.  Male Sprague-Dawley rats were evaluated in the novel object recognition (NOR) task to determine whether novel Sal A analogues impair long term recognition memory. The degree of novelty was also investigated on a cellular basis through quantifying c-Fos immunoreactive neurons within the perirhinal cortex, an area of the brain shown to respond to novelty.  Acute administration of Sal A (0.3 and 1 mg/kg) and novel analogues Ethy Sal A (0.3 and 1 mg/kg), Mesyl Sal B (0.3 and 1 mg/kg), and Bromo Sal A (1 mg/kg) showed no significant differences compared to vehicle when tested in the NOR task. The prototypical KOPr agonist, U50,488 (10 mg/kg), produced a significant decrease in recognition index compared to vehicle when tested in the same task as the novel analogues. Correlating the recognition indices calculated from U50,488 in the NOR to c-Fos counts in the perirhinal cortex showed a strong positive correlation with an increase in RI relating to an increase in c-Fos activation. U50,488 (10 mg/kg) showed a non-significant trend compared to vehicle in the number of c-Fos immunoreactive cells within the perirhinal cortex.  Neither Sal A nor novel analogues affected NOR, suggesting no impairment of long term recognition memory. The lack of this side-effect, among others, demonstrates that the development of potent KOPr agonists with reduced side-effect profiles is feasible. These novel analogues show improvement over the traditional KOPr agonists.</p>

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