Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists

  title={Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists},
  author={Pascale Mazzola-Pomietto and Charanjit Singh Aulakh and Teresa J. Tolliver and Dennis L. Murphy},
Abstract In the present study, we investigated the duration of attenuation of the temperature increases produced by (±) 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and m-chlorophenylpiperazine (m-CPP) which followed pretreatment with four serotonin (5-HT) antagonists; metergoline, mesulergine, mianserin and ritanserin. The duration of attenuation of m-CPP-induced hyperthermia lasted less than 1 day for ritanserin, more than 1 day for the 5 mg/kg doses of both mianserin and metergoline… 

Assessment of the serotonin reuptake blocking property of YM992: Electrophysiological studies in the rat hippocampus and dorsal raphe

The results showed that YM992 attenuated the inhibitory effect of intravenous administration of LSD and the 5‐HT1A agonist 8‐OH‐DPAT on the firing activity of 5‐ HT neurons, and markedly increased the effectiveness of the electrical stimulation of ascending 5-HT fibres on firingActivity of the postsynaptic hippocampus pyramidal neurons.

In vivo electrophysiological examination of 5-HT2 responses in 5-HT2C receptor mutant mice

The present results indicate that the inhibitory action of DOI is predominantly mediated by the 5-HT2A receptor in the OFC, and that DOI and mCPP might be acting in the caudate nucleus through an atypical 5- HT2 receptor yet to be characterized.

Imaging Brain Phospholipase A2 Activation in Awake Rats in Response to the 5-HT2A/2C Agonist (±)2,5-Dimethoxy-4-Iodophenyl-2-Aminopropane (DOI)

The results suggest that the 5-HT2 syndrome involves widespread brain activation of PLA2 via 5- HT2A receptors, leading to the release of the second messenger, arachidonic acid, in unanesthetized adult rats.

Pharmacological characterization of the effects of 3,4-methylenedioxymethamphetamine ("ecstasy") and its enantiomers on lethality, core temperature, and locomotor activity in singly housed and crowded mice

The MDMA isomers have heterogeneous effects that can be demonstrated across a wide range of endpoints and were differentially attenuated by the various serotonergic pretreatments and manipulation of the ambient temperature across housing conditions.

A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats results in a long term defect in thermoregulation

A neurotoxic dose of MDMA resulted in impaired thermoregulation when rats were exposed to high ambient temperature, and impaired serotonergic function following MDMA presumably alters the neurotransmitter balance, thereby compromising thermoreGulation.

The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives

TheHyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach.



Evidence that 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane-induced hypophagia and hyperthermia in rats is mediated by serotonin-2A receptors.

Findings suggest that DOM-induced hypophagia and hyperthermia in rats are mediated by stimulation of 5-HT2a receptors.

Adaptation of brain 5HT2 receptors after mianserin treatment: receptor sensitivity, not receptor binding, more accurately correlates with behavior.

The time course for recovery of 5HT2 receptor sensitivity corresponded more closely to behavioral recovery than did 5HT1 receptor binding, and changes in both receptor density and receptor sensitivity were investigated as possible mechanisms of mianserin's prolonged activity.

Effects of various serotonin receptor subtype-selective antagonists alone and on m-chlorophenylpiperazine-induced neuroendocrine changes in rats.

Findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5- HT3 receptor subtype or by nonserotonergic mechanisms.

Serotonin receptor sensitivity after acute and chronic treatment with mianserin.

The chronic administration of mianserin for 14 days leads to a marked decrease in the maximal number of serotonin2 (5-HT2) binding sites in brains of rats and mice with no change in the KD values.

Regulation of 5-HT2 and 5-HT1C serotonin receptor levels. Methodology and mechanisms.

  • B. RothM. HamblinR. Ciaranello
  • Biology, Psychology
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
  • 1990
Preliminary information suggests that developmentally induced alterations in 5-HT2 and5-HT1c receptors may be due to transcriptional regulation while changes caused by mianserin treatment might bedue to posttranslational processes.

Potencies of antagonists indicate that 5‐HT1C receptors mediate 1–3(chlorophenyl)piperazine‐induced hypophagia

Results strongly support the hypothesis that mediation of mCPP‐induced hypophagia is by stimulation of 5‐HT1C receptors and the mediation of 4‐HT2‐induced head twitches by 5‐ HT2 receptors.