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Modification of the behavioral effects of morphine in rats by serotonin (5-HT) sub(1A) and 5-HT sub(2A) receptor agonists: antinociception, drug discrimination, and locomotor activity

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-HT sub(1A) and 5-HT... Full description

Journal Title: Psychopharmacology 2013, Vol.225 (4), p.791-801
Main Author: Li, Jun-Xu
Other Authors: Shah, Aparna P , Patel, Sunny K , Rice, Kenner C , France, Charles P
Format: Electronic Article Electronic Article
Language: English
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ID: ISSN: 0033-3158
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recordid: cdi_proquest_miscellaneous_1291606704
title: Modification of the behavioral effects of morphine in rats by serotonin (5-HT) sub(1A) and 5-HT sub(2A) receptor agonists: antinociception, drug discrimination, and locomotor activity
format: Article
creator:
  • Li, Jun-Xu
  • Shah, Aparna P
  • Patel, Sunny K
  • Rice, Kenner C
  • France, Charles P
subjects:
  • Primates
ispartof: Psychopharmacology, 2013, Vol.225 (4), p.791-801
description: 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-HT sub(1A) and 5-HT sub(2A) 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-HT sub(2A) agonist) and 8-OH-DPAT (5-HT sub(1A) 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-HT sub(2A) 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-HT sub(1A) receptor-selective antagonist WAY100635. Conclusion: Agonists acting at 5-HT sub(1A) or 5-HT sub(2A) 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.
language: eng
source:
identifier: ISSN: 0033-3158
fulltext: no_fulltext
issn:
  • 0033-3158
  • 1432-2072
url: Link


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titleModification of the behavioral effects of morphine in rats by serotonin (5-HT) sub(1A) and 5-HT sub(2A) receptor agonists: antinociception, drug discrimination, and locomotor activity
creatorLi, Jun-Xu ; Shah, Aparna P ; Patel, Sunny K ; Rice, Kenner C ; France, Charles P
creatorcontribLi, Jun-Xu ; Shah, Aparna P ; Patel, Sunny K ; Rice, Kenner C ; France, Charles P
descriptionRationale: 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-HT sub(1A) and 5-HT sub(2A) 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-HT sub(2A) agonist) and 8-OH-DPAT (5-HT sub(1A) 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-HT sub(2A) 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-HT sub(1A) receptor-selective antagonist WAY100635. Conclusion: Agonists acting at 5-HT sub(1A) or 5-HT sub(2A) 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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titleModification of the behavioral effects of morphine in rats by serotonin (5-HT) sub(1A) and 5-HT sub(2A) receptor agonists: antinociception, drug discrimination, and locomotor activity
authorLi, Jun-Xu ; Shah, Aparna P ; Patel, Sunny K ; Rice, Kenner C ; France, Charles P
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abstractRationale: 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-HT sub(1A) and 5-HT sub(2A) 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-HT sub(2A) agonist) and 8-OH-DPAT (5-HT sub(1A) 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-HT sub(2A) 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-HT sub(1A) receptor-selective antagonist WAY100635. Conclusion: Agonists acting at 5-HT sub(1A) or 5-HT sub(2A) 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.
doi10.1007/s00213-012-2870-2