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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-09-20

AUTHORS

Jun-Xu Li, Aparna P. Shah, Sunny K. Patel, Kenner C. Rice, Charles P. France

ABSTRACT

RationaleIndirect-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.ObjectiveThis 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.MethodsMale 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).ResultsDOM 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.ConclusionAgonists 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. More... »

PAGES

791-801

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00213-012-2870-2

DOI

http://dx.doi.org/10.1007/s00213-012-2870-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000075998

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22993050


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