Behavioral effects of dipropyltryptamine in rats: evidence for 5-HT1A and 5-HT2A agonist activity.
These studies investigated the role of serotonin-1A (5-HT1A) and 5-HT2A receptors in the behavioral effects of dipropyltryptamine (DPT). Eight rats discriminated 0.56 mg/kg 2,5-dimethoxy-4-methylamphetamine (DOM) from saline and responded under a fixed ratio 5 schedule of food presentation; 12 other rats were used for observational studies. DOM and DPT increased responding on the DOM lever with 3.2 mg/kg DPT producing greater than 95% responding on the DOM lever; this effect of DPT was antagonized by the 5-HT2A receptor antagonist MDL100907. In another study, the 5-HT1A and 5-HT7 receptor agonist 8-OH-DPAT produced lower-lip retraction and, at larger doses, flat body posture; DPT alone produced flat body posture and not lower-lip retraction; MDL100907 alone did not produce either effect. Pretreatment with DPT blocked 8-OH-DPAT-elicited lower-lip retraction, suggesting antagonist activity of DPT at 5-HT1A receptors; however, in the presence of MDL100907 DPT produced not only flat body posture but also lower-lip retraction, suggesting that agonist activity of DPT at 5-HT2A receptors masked agonist activity at 5-HT1A receptors. Lower-lip retraction and flat body posture by DPT in the presence of MDL100907 were attenuated by the 5-HT1A receptor antagonist WAY100635. These findings suggest that DPT has agonist activity at 5-HT1A and 5-HT2A receptors and that effects at 5-HT2A receptors mask effects at 5-HT1A receptors.
Li
Jun-Xu
JX
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
Rice
Kenner C
KC
France
Charles P
CP
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004193:Discrimination Learning; D004347:Drug Interactions; D005464:Fluorobenzenes / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011187:Posture; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
D005464:Fluorobenzenes; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C007528:dipropyltryptamine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C079049:volinanserin