Interaction of Morphine and Selective Serotonin Receptor Inhibitors in Rats Experiencing Inflammatory Pain

Lee, Byung-Sang; Jun, In‐Gu; Kim, Sung Hoon; Park, Jong Yeon

doi:10.3346/jkms.2012.27.4.430

Cited by 20 publications

(16 citation statements)

References 32 publications

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“…Furthermore, other adaptive changes within the CNS resulting from the continued receptor stimulation by morphine concern alterations in the expression of different proteins at the cellular level or modifications in the connectivity of neurons involved in the nociception transmission and/or supraespinal integration (Christie, 2008). The antinociceptive-like effect detected after the acute administration of citalopram observed in development of tolerance experiments (Figure 3) has not been consistently described in previous investigations regardless its possible participation as potentiator of morphine analgesia (Fasmer et al, 1989, Larsen and Christensen, 1982, Larsen and Hyttel, 1985, Lee et al , 2012, Sugrue, 1979. The reason for this discrepancy probably resides in the nature of the hot-plate nociception assay where…”

Section: Accepted Manuscriptmentioning

confidence: 71%

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Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects

Varela

Rocha

Díaz

et al. 2017

Pharmacology Biochemistry and Behavior

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Morphine and related opioids are the mainstay of analgesic treatment, especially in patients suffering chronic pain. Besides their antinociceptive effects they may also exhibit anxiolytic-like properties that could contribute to pain relief. The pharmacological manipulation of the serotonergic system may not only modulate pain transmission and processing but also other behavioral effects of opioids. The present study aimed to analyze the effect of the concurrent treatment with citalopram, a selective serotonin reuptake inhibitor, on the antinociceptive, locomotor and anxiety-related effects induced by acute and subchronic administration of morphine in mice. Citalopram (15mg/kg) enhanced the acute antinociceptive effects of morphine when concurrently administered as evidenced by a two-fold increase in the ED for the antinociceptive effect of morphine in the hot-plate test. Chronic studies also revealed that concurrent citalopram treatment (15mg/kg) delayed the development of tolerance to the thermal antinociceptive effects of morphine. Additionally, morphine-induced hyperlocomotion was potentiated by citalopram as assessed in the open-field test and in the spontaneous activity recording in the home cage, a behavioral outcome to which tolerance or desensitization was not developed. Interestingly, chronic administration of both drugs promoted an anxiolytic effect as evidenced by the increased central activity in the open field test. Future investigations on this pharmacological interaction, such as the possible translational research in clinics, might have consequences in future strategies for the therapeutic management of pain.

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Section: Accepted Manuscriptmentioning

confidence: 71%

“…i.e. mianserin and methysergide, suggested the participation of 5-HT 2 receptor subtypes in these processes (Gatch et al, 1998, Lee et al, 2012. At this respect, we after sustained treatments (Berger andWhistler, 2010, Whistler, 2012).…”

Section: Accepted Manuscriptmentioning

confidence: 83%

Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects

Varela

Rocha

Díaz

et al. 2017

Pharmacology Biochemistry and Behavior

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“…For example, administration of the 5-HT precursor 5-hydroxytryptophan (5-HTP) or an SSRI (fluoxetine, citalopram, or paroxetine) increases morphine antinociception in mice and rats, respectively (Dewey et al, 1970, Larson and Takemori, 1977, Hynes et al, 1985; Lee et al, 2012). Moreover, fluoxetine and the 5-HT releaser fenfluramine enhance the antinociceptive effects morphine in nonhuman primates (Gatch et al, 1998; Li et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Modification of the behavioral effects of morphine in rats by serotonin (5-HT)1A and 5-HT2A receptor agonists: antinociception, drug discrimination, and locomotor activity

Shah

Patel

et al. 2012

Psychopharmacology

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Rationale Indirect-acting serotonin (5-HT) receptor agonists can enhance the antinociceptive effects of morphine; however, the specific 5-HT receptor subtype(s) mediating this enhancement is not established. Objective This study examined interactions between morphine and both 5-HT1A and 5-HT2A receptor agonists in rats using measures of antinociception (radiant heat tail flick and warm water tail withdrawal), drug discrimination (3.2 mg/kg morphine versus saline), and locomotion. Methods Male Sprague-Dawley rats (n=7–8 per group) were used to examine the effects of morphine alone and in combination with DOM (5-HT2A agonist) and 8-OH-DPAT (5-HT1A agonist). Results DOM did not modify antinociceptive or discriminative stimulus effects while modestly attenuating locomotor-stimulating effects of morphine; the effect of DOM (0.32 mg/kg) on morphine-induced locomotion was prevented by the 5-HT2A receptor selective antagonist MDL 100907. In contrast, 8-OH-DPAT (0.032–0.32 mg/kg) fully attenuated the antinociceptive effects (both procedures), did not modify the discriminative stimulus effects, and enhanced (0.32 mg/kg) the locomotor-stimulating effects of morphine. These effects of 8-OH-DPAT were prevented by the 5-HT1A receptor selective antagonist WAY100635. Conclusion Agonists acting at 5-HT1A or 5-HT2A receptors do not modify all effects of mu opioid receptor agonists in a similar manner. Moreover, interactions between 5-HT and opioid receptor agonists vary significantly between rats and nonhuman primates, underscoring the value of comparing drug interactions across a broad range of conditions and in multiple species.

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“…In experimental and clinical studies it has been found that antidepressants possess antinociceptive and analgesic properties and are therefore used in the combined therapy of chronic pain. 1 The serotoninselective reuptake inhibitors (SSRIs) were fi rst introduced as a new class of antidepressants at the end of 1980s and due to their favorable side-effect profi le have since become fi rst-line therapy of depressive disorders. 2 Most SSRIs have been found to also possess secondary binding properties -dopamine reuptake inhibition, noradrenaline reuptake inhibition, muscarinic cholinergic antagonism, etc.…”

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confidence: 99%

Experimental Study of the Analgesic Effect of the Antidepressant Escitalopram

Zlatanova¹,

Kandilarov²,

Kostadinov³

et al. 2018

Folia Medica

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Background: Antidepressants have been found to possess antinociceptive and analgesic properties and are prescribed in the treatment of chronic pain. Aim: To evaluate the antinociceptive properties of escitalopram after a single administration. Materials and methods: Forty Wistar rats were used in the study. They were divided into 5 groups (n=8) treated with saline solution (control group), metamizole (150 mg/kg b.w.), escitalopram (5, 10 and 20 mg/kg b.w.) intraperitoneally. The nociceptive tests we used employed thermal (hot plate and plantar test), mechanical (analgesimeter) and chemical (formalin test) stimuli. Criteria for analgesic effect were increased latency in hot plate, plantar test, analgesimeter and decreased paw licking time in formalin test. Results: The reference analgesic metamizole showed significant analgesic effect in all tests excluding the first phase with formalin. Escitalopram in doses of 5 and 20 mg/kg b.w. increased paw withdrawal latency in analgesimeter at 2 hours compared to control. Escitalopram in a dose of 5 mg/kg b.w. increased the duration of the stay on the hot plate at 1 hour, while doses of 10 and 20 mg/kg b.w. significantly increased this indicator at 1 and 3 hours in comparison to the saline treated group. In the plantar test, escitalopram in all used doses significantly increased the nociceptive response latency compared to control. A dose of 5 mg/kg b.w. decreased hind paw licking time during phase 1 of the formalin test, whereas doses of 10 and 20 mg/kg b.w. decreased phase 2 licking time compared to the control group. Conclusion: The antidepressant escitalopram has analgesic properties but they are not dose- or time-dependent.

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Interaction of Morphine and Selective Serotonin Receptor Inhibitors in Rats Experiencing Inflammatory Pain

Cited by 20 publications

References 32 publications

Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects

Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects

Modification of the behavioral effects of morphine in rats by serotonin (5-HT)1A and 5-HT2A receptor agonists: antinociception, drug discrimination, and locomotor activity

Experimental Study of the Analgesic Effect of the Antidepressant Escitalopram

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