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Discriminative stimulus effects of DOM in rhesus monkeys: interactions between 5‐HT1A and 5‐HT2A receptor agonists
Author(s) -
Li JunXu,
Rice Kenner C.,
Koek Wouter,
France Charles P.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.743.3
Subject(s) - 5 ht1a receptor , agonist , receptor , 5 ht receptor , buspirone , 8 oh dpat , pharmacology , serotonin , receptor antagonist , chemistry , 5 ht1 receptor , antagonist , biology , biochemistry
Many drugs acting on serotonin (5‐HT) systems, including 5‐HT releasers and reuptake inhibitors, indirectly activate multiple 5‐HT receptor subtypes; however, the impact of the interactions between these receptors is not fully understood. In rodents, activity at 5‐HT1A receptors enhances actions at 5‐HT2A receptors, although the generality of this finding is unknown. This study examined interactions between 5‐HT receptor agonists in rhesus monkeys discriminating between saline and 0.32 mg/kg of the 5‐HT2A receptor agonist DOM. The selective 5‐HT1A receptor agonists 8‐OH‐DPAT and F13714 shifted the DOM dose response curve to the right and this effect was reversed by the 5‐HT1A receptor antagonist WAY100635. The non‐selective 5‐HT1A receptor agonist buspirone had no effect while the 5‐HT2A receptor agonists 2C‐T‐7 and dipropyltryptamine shifted the DOM dose response curve to the left. Thus, agonism at 5‐HT1A receptors attenuated the discriminative stimulus effects of a drug acting at 5‐HT2A receptors. That this interaction in monkeys may be opposite to what has been observed in rodents underscores the need to examine these interactions under a broader range of conditions and in multiple species. CPF is supported by a Senior Scientist Award (DA17918).