Behavioral effects of dipropyltryptamine (DPT) in rats: role of 5‐HT1A and 5‐HT2A receptors

Abstract

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])