Enhanced responsivity of 5-HT(2A) receptors at warm ambient temperatures is responsible for the augmentation of the 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced hyperthermia.
Gongliang Zhang, Rui Tao
Neuroscience Letters February 18, 2011 DOI: 10.1016/j.neulet.2010.12.028 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Animals (species not stated in the abstract) |
| Intervention | ketanserin |
| Topics | Serotonin |
| Key findings | DOI evoked a large increase in body-core temperature at 32 °C ambient temperature, a small increase at 22 °C and 27 °C, and a significantly reduced response at 12 °C; ketanserin pretreatment completely blocked the ambient temperature-dependent response to DOI. The authors argue these findings support a role for 5-HT2A receptors in the neurotoxic effects of psychogenic drugs, with receptor activity inhibited by cold and enhanced by warm ambient temperature. |
Abstract
Warm ambient temperature facilitates hyperthermia and other neurotoxic responses elicited by psychogenic drugs such as MDMA and methamphetamine. However, little is known about the neural mechanism underlying such effects. In the present study, we tested the hypothesis that a warm ambient temperature may enhance the responsivity of 5-HT(2A) receptors in the central nervous system and thereafter cause an augmented response to 5-HT(₂A) receptor agonists. This hypothesis was tested by measuring changes in body-core temperature in response to the 5-HT(2A) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) administered at four different ambient temperature levels: 12 °C (cold), 22 °C (standard), 27 °C (thermoneutral zone) and 32 °C (warm). It was found that DOI only evoked a small increase in body-core temperature at the standard (22 °C) or thermoneutral ambient temperature (27 °C). In contrast, there was a large increase in body-core temperature when the experiments were conducted at the warmer ambient temperature (32 °C). Interestingly, the effect of DOI at the cold ambient temperature of 12 °C was significantly reduced. Moreover, the ambient temperature-dependent response to DOI was completely blocked by pretreatment with the 5-HT(₂A) receptor antagonist ketanserin. Taken together, these findings support the hypothesis that 5-HT(₂A) receptors may be responsible for some neurotoxic effects of psychogenic drugs in the central nervous system, the activity of which is functionally inhibited at cold but enhanced at warm ambient temperature in contrast to that at standard experimental conditions.
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 4
- Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response Biomedicine & Pharmacotherapy August 29, 2022
- Differential role of dose and environment in initiating and intensifying neurotoxicity caused by MDMA in rats BMC Pharmacology and Toxicology August 5, 2019
- Hyperthermia Severely Affects the Vascular Effects of MDMA and Metabolites in the Human Internal Mammary Artery In Vitro. Cardiovascular toxicology October 2017
- The effects of mirtazapine and fluoxetine on hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats. Neuroscience Letters July 15, 2011
Cites 3
- Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Journal of Neuroscience July 1, 1998
- Tolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges. Neuroscience March 27, 2008
- The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens. Pharmacology, Biochemistry, and Behavior April 1998