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Behavioral effects of dipropyltryptamine (DPT) in rats: role of 5‐HT1A and 5‐HT2A receptors
Author(s) -
Li JunXu,
Rice Kenner,
France Charles P.
Publication year - 2007
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.21.6.a780-d
Subject(s) - agonist , 5 ht1a receptor , antagonist , 8 oh dpat , pharmacology , receptor , saline , receptor antagonist , chemistry , 5 ht receptor , partial agonist , medicine , serotonin , endocrinology , psychology
Synthesized in 1950 and reported to have hallucinogenic effects, dipropyltryptamine (DPT) has been studied relatively little in humans or in non‐humans. The limited literature on DPT suggests that it has moderate affinity and low efficacy at 5‐HT1A receptors. This study examined the behavioral effects of DPT in rats. Eight rats discriminated 0.56 mg/kg of 2,5‐dimethoxy‐4‐methylamphetamine (DOM) from saline while responding under a fixed‐ratio schedule of food presentation. DOM and DPT dose‐dependently increased responding on the DOM lever with doses of 0.56 mg/kg of DOM and 3.2 mg/kg of DPT producing greater than 95% responding on the DOM lever. These discriminative stimulus effects of DOM and DPT were antagonized similarly by the selective 5‐HT2A receptor antagonist MDL100907. In a different group of rats (n=12), the 5‐HT1A receptor agonist 8‐OH‐DPAT produced lower lip retraction (LLR) and, at larger doses, flat body posture (FBP). These effects of 8‐OH‐DPAT were not antagonized by MDL100907. DPT (0.32–10 mg/kg) alone produced FBP and not LLR and in combination fully blocked 8‐OH‐DPAT‐elicited LLR. However, in combination with 0.1 mg/kg of MDL100907, DPT (1.0–32 mg/kg) produced LLR; the same dose of MDL100907 partially attenuated DPT‐induced FBP. Finally, the LLR that emerged when DPT was administered in combination with MDL100907 was fully blocked by the 5‐HT1A receptor antagonist WAY100635. Collectively, these findings provide behavioral evidence that DPT has agonist activity at 5‐HT1A and 5‐HT2A receptors, although its agonist effects at 5‐HT1A receptors appear to mask its agonist effects at 5‐HT2A receptors. (CPF is supported by a Senior Scientist Award [DA 17918])