Subsensitivity of serotonin and substance P receptors involved in nociception after repeated administration of a serotonin receptor agonist.
Journal of Neural Transmission 1989 DOI: 10.1007/BF01255814 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | 5-MeODMT 8-OH-DPAT serotonin substance P |
| Dose | 3 mg/kg 5-MeODMT every 30 min for 4 hours; 3 mg/kg 5-MeODMT (test dose); 0.5 mg/kg 8-OH-DPAT; 4.0 micrograms serotonin; 2.5, 5, and 10 ng substance P |
| Duration | 4 hours of repeated 5-MeODMT administration, with testing 90-120 minutes after the last injection |
| Topics | Serotonin |
| Citations | 9 |
| Key findings | Repeated administration of 5-MeODMT reduces the antinociceptive effects of 5-MeODMT and 8-OH-DPAT and attenuates behavioral responses to intrathecal serotonin and substance P, suggesting downregulation of serotonin receptors and a functional interaction between serotonin and substance P in spinal pain modulation. |
Abstract
The antinociceptive effects of subcutaneous 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the responses to intrathecal (i.th.) serotonin (5-HT) and substance P (SP) were examined in mice after repeated administration of 5-MeODMT (3 mg/kg every 30 min for 4 hours). Ninety min after the last injection of 5-MeODMT the basal tail-flick and hot-plate response latencies were unaltered, but the antinociceptive effects of 5-MeODMT (3 mg/kg) in the tail-flick and hot-plate tests and the antinociceptive effect of 8-OH-DPAT (0.5 mg/kg) in the hot-plate test were markedly reduced. The behavioral responses to i.th. 5-HT (4.0 micrograms) and SP (2.5, 5, and 10 ng) which include vigorous biting, licking and scratching of the caudal part of the body, were attenuated 90-120 min after withdrawal of 5-MeODMT treatment. It is suggested that repeated administration of 5-MeODMT downregulates the function of the 5-HT receptors mediating the antinociceptive effects of 5-MeODMT and 8-OH-DPAT. The rapid desensitization to the behavioral responses both to 5-HT and SP by 5-MeODMT pretreatment may reflect a functional interaction between 5-HT and SP in the spinal modulation of nociception.
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| 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
Cites 6
- Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat European Journal of Pharmacology October 1, 1985
- In vivo metabolism of 5-methoxy-N,N-dimethyltryptamine and N,N-dimethyltryptamine in the rat. Biochemical Pharmacology May 1, 1987
- Development of selective tolerance to the serotonin behavioral syndrome and suppression of locomotor activity after repeated administration of either 5-MeODMT or mCPP. Life Sciences July 1, 1985
- (+)-8-OH-DPAT and 5-MeODMT induced analgesia is antagonised by noradrenaline depletion. Physiology & Behavior 1987
- Development of tolerance to repeated administration of 5-methoxy-N,N-dimethyltryptamine in rats. European Journal of Pharmacology January 15, 1985
and 1 more in the library