Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors.
N S Buckholtz, D F Zhou, D X Freedman
Life Sciences 1988 DOI: 10.1016/0024-3205(88)90342-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study (rat, in vivo receptor binding) Peer reviewed |
|---|---|
| Population | Rat brain (5-HT2 receptor binding) |
| Interventions | DOI DOB LSD |
| Dose | DOI 1.0 mg/kg or 7.0 mg/kg; DOB 0.5 mg/kg; LSD 130 µg/kg or 650 µg/kg |
| Duration | 7 days of daily administration; binding assessed 4 and 24 hours after single doses |
| Measures | [3H]ketanserin binding |
| Topics | Serotonin |
| Key points | Daily DOI (1.0 mg/kg) or DOB (0.5 mg/kg) for 7 days decreased 5-HT2 receptor binding in rat brain, similar to the decrease seen after LSD. A single low dose of LSD (130 µg/kg) or DOI (1.0 mg/kg) did not change binding at 24 hours, whereas a single high dose (LSD 650 µg/kg; DOI 7.0 mg/kg) reduced binding at both 4 and 24 hours. The authors conclude that 5-HT2 agonists down-regulate 5-HT2 receptors and that LSD acts in a parallel fashion. |
Abstract
Daily administration of D-lysergic acid diethylamide (LSD) was previously shown to decrease serotonin2 (5-HT2) receptor binding in rat brain. Recently, 4-substituted derivatives of 1-(2,5-dimethoxyphenyl)-2-aminopropane, the substitution being with either iodine (DOI) or bromine (DOB), have been suggested to be relatively selective 5-HT2 agonists. These compounds share common behavioral and neurophysiological effects with LSD, suggested to be 5-HT2 receptor mediated, and the purpose of the present study was to determine whether they also affect 5-HT2 receptor binding after systemic administration in a similar way to LSD. Administration of DOI (1.0 mg/kg) or DOB (0.5 mg/kg) for 7 days resulted in a decrease in 5-HT2 binding, as evaluated with [3H]ketanserin, similar to the decrease after LSD. In a further evaluation of the parallelism of LSD and 5-HT2 agonists, it was found that 24 hr after one administration of a low dose of LSD (130 ug/kg) or DOI (1.0 mg/kg), there was no change in binding, but there was a decrease 24 hr after a high dose (LSD, 650 micrograms/kg; DOI, 7.0 mg/kg). Four hours after the high dose of LSD or DOI there was also a decrease in 5-HT2 binding. Thus, results have shown that 5-HT2 agonists are capable of down-regulating 5-HT2 receptors and that LSD acts in a parallel fashion. This study has also demonstrated that 5-HT2 receptors can be modified within hours after drug administration.
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
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- 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Journal of Neuroscience April 15, 1997
- Therapeutic effects of classic serotonergic psychedelics: A systematic review of modern‐era clinical studies Acta Psychiatrica Scandinavica October 30, 2020
- A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain International Journal of Molecular Sciences January 15, 2021
- Recreational use of psychedelics is associated with elevated personality trait openness: Exploration of associations with brain serotonin markers. Journal of Psychopharmacology February 28, 2019
and 28 more in the library
Cites 11
- Evidence for 5-HT2 involvement in the mechanism of action of hallucinogenic agents. Life Sciences December 17, 1984
- Phenethylamine hallucinogens in the locus coeruleus: potency of action correlates with rank order of 5-HT2 binding affinity European Journal of Pharmacology December 1, 1986
- Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens. Psychopharmacology 1988
- Effect of hallucinogens on spontaneous and sensory-evoked locus coeruleus unit activity in the rat: reversal by selective 5-HT2 antagonists. Brain Research October 1, 1986
- Discriminative stimulus properties of the serotonergic agent 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Life Sciences September 1, 1986
and 6 more in the library