Differential effects of serotonin 5-HT1A receptor agonists on the discriminative stimulus effects of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rats and rhesus monkeys.
Jun-Xu Li, Wouter Koek, Kenner C Rice, Charles P France
Journal of Pharmacology and Experimental Therapeutics April 1, 2010 DOI: 10.1124/jpet.109.163451 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Comparative animal model study Peer reviewed |
|---|---|
| Sample size | 11 |
| Population | 8 rats and 3 rhesus monkeys |
| Interventions | 1-(2 5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (8-OH-DPAT) 3-chloro-4-fluorophenyl-(4-fluoro-4-([(5-methyl-6-methylaminopyridin-2-ylmethyl) amino) methyl] piperidin-1-yl) methanone (F13714) 2 5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) dipropyltryptamine (DPT) N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) |
| Dose | 0.56 mg/kg i.p. DOM for rats, 0.32 mg/kg s.c. DOM for monkeys |
| Topics | Serotonin |
| Keywords | Species differences Interspecies variation Comparative pharmacology Animal model differences Species-specific effects Cross-species variation Neurobiology Serotonin receptors 5-HT Receptors Receptor pharmacology 5-ht1a 5-ht2a Receptor agonists Drug interactions Pharmacological interactions Multi-target drug mechanisms Drug modulation Drug combination effects Animal models Preclinical research Rat model Monkey model Rhesus monkeys Behavioral pharmacology |
| Citations | 17 |
| Key points | 5-HT1A receptor agonists attenuated the discriminative stimulus effects of the 5-HT2A agonist DOM in monkeys but not in rats, revealing a species difference in 5-HT receptor interactions. |
Abstract
Although many drugs act by indirectly stimulating multiple receptors (e.g., reuptake inhibitors), relatively little is known about interactions between agonism at different receptors. This study compared the effect of serotonin (5-HT)(1A) receptor agonists with the discriminative stimulus effects of the 5-HT(2A) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in rats and rhesus monkeys. Eight rats discriminated 0.56 mg/kg i.p. DOM and responded under a fixed ratio (FR) 10 schedule of food presentation, whereas three rhesus monkeys discriminated 0.32 mg/kg s.c. DOM and responded under an FR 5 schedule of stimulus shock termination. DOM and the 5-HT(2A) receptor agonists 2,5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) and dipropyltryptamine (DPT), but not the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin hydrochloride (8-OH-DPAT) and 3-chloro-4-fluorophenyl-(4-fluoro-4-([(5-methyl-6-methylaminopyridin-2-ylmethyl) amino) methyl] piperidin-1-yl) methanone (F13714), occasioned responding on the DOM-associated lever in rats and monkeys. Both 8-OH-DPAT and F13714 attenuated the discriminative stimulus effects of DOM in monkeys but not in rats; these effects of 8-OH-DPAT and F13714 were prevented by the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635). DPT and 2C-T-7 enhanced the discriminative stimulus effects of DOM in rats and monkeys in an additive manner. Taken together, the results suggest that the DOM discriminative stimulus is pharmacologically similar and mediated by 5-HT(2A) receptors in rats and monkeys; however, the ability of 5-HT(1A) receptor agonists to modify the effects of DOM is markedly different between these species. These results indicate possible differences in the neurobiology of 5-HT systems that could be important for studying drugs that have multiple mechanisms of action (e.g., reuptake inhibitors that indirectly stimulate multiple receptors).
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 8
- Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function. Psychopharmacology March 1, 2014
- Return of the lysergamides. Part IV: Analytical and pharmacological characterization of lysergic acid morpholide (LSM‐775) Drug Testing and Analysis June 5, 2017
- Locomotor and discriminative stimulus effects of four novel hallucinogens in rodents. Behavioural Pharmacology August 1, 2017
- Use of the head-twitch response to investigate the structure–activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines Psychopharmacology December 7, 2022
- The Emergence of Isotryptamine Analogs as Novel Serotonergic Agents with Psychotherapeutic Potential ACS Pharmacology & Translational Science August 18, 2026
and 3 more in the library
Cites 11
- Do functional relationships exist between 5-HT1A and 5-HT2 receptors? Pharmacology, Biochemistry, and Behavior August 1, 1990
- Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics February 1, 2008
- Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys: antagonism and apparent pA2 analyses. Journal of Pharmacology and Experimental Therapeutics March 1, 2009
- Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), ketanserin, and (R)-(+)-{alpha}-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907) in rats. Journal of Pharmacology and Experimental Therapeutics November 2009
- Effect of 8-hydroxy-2-(N,N-di-n-propylamino)tetralin and MDMA on the discriminative stimulus effects of the classical hallucinogen DOM in rats. Pharmacology, Biochemistry, and Behavior August 17, 2008
and 6 more in the library