The stimulus effects of 8-OH-DPAT: evidence for a 5-HT2A receptor-mediated component.
Chad J Reissig, Justin R Eckler, R A Rabin, K C Rice, Jerrold C Winter
Pharmacology, Biochemistry, and Behavior September 19, 2007 DOI: 10.1016/j.pbb.2007.09.011 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study in rats Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Male Fischer 344 rats |
| Interventions | 8-OH-DPAT buspirone WAY-100635 M100907 |
| Dose | 8-OH-DPAT 0.2 mg/kg; M100907 0.1 mg/kg |
| Topics | LSD Serotonin |
| Keywords | Animals Rats, inbred f344 Fluorobenzenes Piperazines Piperidines Pyridines Buspirone 8-hydroxy-2-di-n-propylaminotetralin Receptor, serotonin, 5-ht1a Receptor, serotonin, 5-ht2a Serotonin antagonists Dose-response relationship, drug Male Serotonin receptor agonists Discrimination, psychological |
| Key points | The 5-HT1A antagonist WAY-100635 completely blocked stimulus control by 8-OH-DPAT and its generalization to buspirone, whereas the 5-HT2A antagonist M100907 produced significant but incomplete blockade. The authors argue this indicates bidirectional interaction between 5-HT1A and 5-HT2A receptors in drug discrimination. |
Abstract
A previous investigation in our laboratory found that the stimulus effects of the 5-HT2A agonist, LSD, are potentiated by 5-HT1A receptor agonists including the prototypic agonist, 8-OH-DPAT. Also suggestive of behaviorally relevant interactions between 5-HT1A and 5-HT2A receptors are behavioral analyses of locomotor activity, head-twitch response, forepaw treading and production of the serotonin syndrome; in some instances effects are augmented, in other, diminished. These observations led us in the present investigation to test the hypothesis that stimulus control by 8-OH-DPAT [0.2 mg/kg; 15 min pretreatment time] is modulated by 5-HT2A ligands. Stimulus control was established with 8-OH-DPAT in a group of 10 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. As shown previously, stimulus control by 8-OH-DPAT and the generalization of 8-OH-DPAT to the 5-HT1A partial agonist, buspirone, was completely blocked by the selective 5-HT1A antagonist, WAY-100635. In contrast, antagonism by the selective 5-HT2A antagonist, M100907 [0.1 mg/kg; 30 min pretreatment time], of 8-OH-DPAT and of the generalization of 8-OH-DPAT to buspirone was statistically significant but less than complete. In light of our previous conclusions regarding the interactions of 5-HT1A agonists with LSD-induced stimulus control, the present data suggest that the interaction between 5-HT1A and 5-HT2A receptors is bidirectional in drug discrimination studies.
Comparable studies
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| 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 | |
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| 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 4
- The Emergence of Isotryptamine Analogs as Novel Serotonergic Agents with Psychotherapeutic Potential ACS Pharmacology & Translational Science August 18, 2026
- Historical Perspectives and Pharmacodynamic Actions of the Magic Mushroom (Psilocybin) for Future Global Healthcare Trends in Medical Research June 28, 2024
- The renaissance in psychedelic research: What do preclinical models have to offer. Progress in Brain Research 2018
- Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology April 2009
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and 3 more in the library