Potentiation of κ-opioid receptor agonist-induced analgesia and hypothermia by fluoxetine

Nemmani, Kumar V.S.; Gullapalli, Srinivas; Ramarao, P.

doi:10.1016/s0091-3057(01)00537-8

Cited by 22 publications

(12 citation statements)

References 10 publications

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“…In the present study, the selective -agonist U50,488H produced a dose-dependent hypothermic response, with a maximum decrease in Tb induced by 10 mg/kg. The data are in line with previous studies showing that the -opioid receptor is involved in hypothermia (Adler et al, 1988;Nemmani et al, 2001). Although there is evidence of -involvement, little is known about its mechanism of action.…”

Section: Discussionsupporting

confidence: 92%

“…Since the hypothermic effect of U50,488H, a -opioid agonist, was blocked by nor-BNI, a selective -opioid antagonist (Xin et al, 1997), the effect of U50,488H on body temperature must be by a -mediated mechanism. It was demonstrated recently that the hypothermia induced by U50,488H is potentiated by a selective 5-HT inhibitor, suggesting a role of 5-HT in the mediation of hypothermia (Nemmani et al, 2001). Also, U50,488H-induced hypothermia was potentiated by pretreatment with chlorpromazine, indicating that biogenic amines can interact with the -opioid-receptor-mediated hypothermia .…”

Section: Discussionmentioning

confidence: 96%

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Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats

Benamar

Geller²,

Adler³

2002

J Pharmacol Exp Ther

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The effect of central and peripheral administration of a nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the hypothermia induced by the selective -opioid receptor agonist trans-(Ϯ) 3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methane sulfate (U50,488H) was studied in male Sprague-Dawley rats. In the first series of experiments, we examined the effect of subcutaneous (s.c.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME, at a dose of 50 mg/kg s.c., had no influence on body temperature (Tb). Coadministration of L-NAME (50 mg/ kg, s.c.) with U50,488H (10 mg/kg, s.c.) blocked the hypothermia induced by U50,488H. In the second series of experiments, we investigated the effect of intracerebroventricular (i.c.v.) administration of L-NAME on the hypothermia induced by s.c. injection of U50,488H. L-NAME itself, given i.c.v. at a dose of 1 mg/rat, did not evoke any change in Tb. Administration of L-NAME (1 mg/rat, i.c.v.) caused a significant suppression of U50,488H hypothermia. The results indicate that either central or peripheral nitric oxide synthesis is required for the production of hypothermia induced by U50,488H.The endogenous opioid system serves several physiological functions, including a role in temperature regulation. Three distinct opioid receptors (, , and ␦) have been identified. Opioid agonists have been investigated in terms of their ability to alter Tb (Clark et al., 1983;Geller et al., 1983Geller et al., , 1986, the response being dependent upon a number of factors including species, strain, dosage, route of administration, ambient temperature, and receptor selectivity (Adler et al., 1988). Previous results from this and other laboratories demonstrated that i.c.v. administration of selective -receptor agonists produced hyperthermia (Spencer et al., 1988;Handler et al., 1992;Adler and Geller, 1993), whereas -receptor agonists produced hypothermia Spencer et al., 1988).Nitric oxide (NO), recently recognized as a prominent second messenger (Breder and Saper, 1996), is produced by the enzyme nitric-oxide synthase (NOS) that uses L-arginine to make L-citruline and the radical gas NO. NO has been found in peripheral and central neurons (Breder and Saper, 1996). Three different isoforms of NOS have been described (LopezFigueroa et al., 1998). Two are constitutive forms, endothelial and neuronal (Moncada et al., 1991), and the third is inducible (Lowenstein et al., 1992). Within the last few years, a number of studies have been conducted to investigate whether NO plays a role in temperature regulation, fever, and hypothermia. Some authors have suggested that NO has an antipyretic function (Moncada et al., 1991;Gourine, 1995), and some have shown that NO is involved in hypothermia (Branco et al., 1997;Steiner et al., 1998;Almeida and Branco, 2001). However, other articles provide evidence that the formation of NO participates in the development of a febrile response (Lin and Lin, 1996;Scammell et al., 19...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats

Benamar

Geller²,

Adler³

2002

J Pharmacol Exp Ther

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“…Hypothermic effects have been reported for the k opioid receptor agonists U50488, U69593, and salvinorin A (Hayes et al, 1985;Cavicchini et al, 1989;Nemmani et al, 2001;Baker and Meert, 2002), and there is a report of spiradoline producing hypothermia after intracerebroventricular administration (Adler and Geller, 1993). The present study generated full dose-response functions for the hypothermic effects of spiradoline after i.p.…”

Section: Discussionmentioning

confidence: 79%

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Minervini¹,

Dahal²,

France³

2016

J Pharmacol Exp Ther

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Pain is a significant clinical problem, and there is a need for more effective treatments with reduced adverse effects that currently limit the use of m opioid receptor agonists. Synthetic k opioid receptor agonists have no abuse liability and well-documented antinociceptive effects; however, adverse effects (diuresis, dysphoria) preclude their use in the clinic. Combining k opioids with nonopioid drugs (cannabinoid receptor agonists) allows for smaller doses of each drug to produce antinociception. This study tested whether a potentially useful effect of the k opioid receptor agonist 2-Cumulative dose-response functions were determined in eight male Sprague-Dawley rats for spiradoline (0.032-32.0 mg/kg, i.p.) and CP55940 (0.0032-1.0 mg/kg, i.p.) for antinociception, hypothermia, food-maintained responding, and diuresis. Alone, each drug dose dependently increased tail withdrawal latencies from 50°C water, decreased body temperature by ∼4°C, and eliminated food-maintained responding. Spiradoline, but not CP55940, significantly increased urine output at doses that eliminated responding. Smaller doses of spiradoline and CP55940 in mixtures (3:1, 1:1, and 1:3 spiradoline:CP55940) had effects comparable to those observed with larger doses of either drug administered alone: the interaction was additive for antinociception and additive or greater than additive for hypothermia and food-maintained responding. Collectively, these data fail to provide support for the use of these mixtures for treating acute pain; however, k opioid/cannabinoid mixtures might be useful for treating pain under other conditions (e.g., chronic pain), but only if the adverse effects of both drugs are not enhanced in mixtures.

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“…Previous studies have suggested that serotonin plays an important role in opioid-mediated analgesia. [2829] One of the studies reported that fluoxetine (a selective serotonin reuptake inhibitor) suppressed the dependence and development of tolerance to the antinociceptive effect of morphine. [30] In another study, it has been stated that systemically administered morphine activates the serotonergic pathways and 5-HT 7 receptors in the spinal cord play an important role in the systemic morphine antinociception.…”

Section: Discussionmentioning

confidence: 99%

Zimelidine attenuates the development of tolerance to morphine-induced antinociception

et al. 2012

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Objectives:The aim of this study was to investigate effect of zimelidine (a serotonin reuptake inhibitor) on morphine-induced tolerance in rats.Materials and Methods:Male Wistar albino rats weighing 160–180 g were used in these experiments (n=72). A 3-day cumulative dosing regimen was used for the induction of morphine tolerance. To constitute of morphine tolerance, animals received morphine twice daily for 3 days. After the last dose morphine was injected on the fourth day, morphine tolerance was evaluated. The analgesic effects of zimelidine (15 mg/kg; i.p.) and morphine (5 mg/kg) were considered at 30-min time intervals (0, 30, 60, 90 and 120 min) by tail-flick and hot-plate analgesiometer (n=6 in each experimental group).Results:The results showed that zimelidine significantly attenuated the development and expression of morphine tolerance. The maximal antinociceptive effect of zimelidine was obtained at the 60 minutes measurements in the zimelidine group and at the 30 minutes measurements in the morphine tolerant group by the tail-flick and hot-plate tests. Administration of zimelidine with morphine showed additive analgesic effect.Conclusion:In conclusion, our results show that zimelidine reduces the development of tolerance to morphine-induced antinociception in rats.

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Potentiation of κ-opioid receptor agonist-induced analgesia and hypothermia by fluoxetine

Cited by 22 publications

References 10 publications

Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats

Role of the Nitric Oxide Pathway in κ-Opioid-Induced Hypothermia in Rats

Behavioral Characterization of κ Opioid Receptor Agonist Spiradoline and Cannabinoid Receptor Agonist CP55940 Mixtures in Rats

Zimelidine attenuates the development of tolerance to morphine-induced antinociception

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