The Journal of pharmacology and experimental therapeutics
February 1, 2008
Jun-Xu Li, Kenner C Rice, Charles P France
51 citations
In rhesus monkeys trained to distinguish the hallucinogen DOM from a placebo, the drug's effects lasted up to two hours and were blocked by serotonin 5-HT2A receptor antagonists but not by the dopamine antagonist haloperidol. Other hallucinogens such as LSD and 2C-T-7 produced DOM-like effects, but the kappa-opioid hallucinogen salvinorin A did not, nor did several other psychoactive drugs. These results confirm that 5-HT2A receptors play a key role in the discriminative stimulus effects of certain hallucinogens in nonhuman primates, and they reveal that different classes of hallucinogens produce qualitatively distinct effects.
The Journal of pharmacology and experimental therapeutics
April 1, 2010
Jun-Xu Li, Wouter Koek, Kenner C Rice et al.
17 citations
Serotonin (5-HT)1A receptor agonists attenuated the effects of the 5-HT2A receptor agonist DOM in rhesus monkeys but not in rats, indicating a species difference in how these receptor systems interact. DOM and other 5-HT2A agonists produced similar discriminative stimulus effects in both species, and these effects were blocked by a 5-HT2A antagonist. The 5-HT1A agonists 8-OH-DPAT and F13714 reduced DOM's effects only in monkeys, an effect prevented by a 5-HT1A antagonist. The findings suggest that while the DOM stimulus is mediated by 5-HT2A receptors in both species, the modulatory role of 5-HT1A receptors differs markedly between rats and monkeys, which has implications for studying drugs with multiple mechanisms.
The Journal of pharmacology and experimental therapeutics
March 1, 2009
Jun-Xu Li, Kenner C Rice, Charles P France
16 citations
In rhesus monkeys trained to distinguish the hallucinogen DOM from a placebo, three related compounds—DOM, 2C-T-7, and DPT—all produced dose-dependent increases in drug-appropriate responding. Three antagonists (MDL100907, ketanserin, and ritanserin) each shifted the dose-response curves of all three agonists rightward in a parallel, competitive manner. The calculated apparent affinities (pA₂ values) for each antagonist were similar across agonists and correlated with their binding affinities at 5-HT₂A receptors, not at 5-HT₂C or alpha₁ adrenergic receptors. These results provide quantitative evidence that the 5-HT₂A receptor subtype predominantly, if not exclusively, mediates the discriminative stimulus effects of these hallucinogenic drugs in rhesus monkeys.