The serotonin 5-HT2A receptor agonist TCB-2: a behavioral and neurophysiological analysis

  title={The serotonin 5-HT2A receptor agonist TCB-2: a behavioral and neurophysiological analysis},
  author={Meredith A. Fox and Helen T. French and Justin L. LaPorte and Adele R. Blackler and Dennis L. Murphy},
RationaleThere are few reports on the high-affinity 5-HT2A agonist (4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).ObjectivesHere we provide the first behavioral and neurophysiological profile of TCB-2 in C57BL/6J mice, with direct comparisons to the 5-HT2A/2C agonist (±)-2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), in addition to determinations of 5-HT2A mediation via pretreatment with the selective 5-HT2A antagonist MDL 11,939.ResultsIn a dose-dependent manner… 

Pharmacological and behavioral characterization of the 5-HT2A receptor in C57BL/6N mice

The current chronic agonist treatment study demonstrated an important similarity between the 5-HT2A receptor in mice, rats, and rabbits, while antagonist treatment revealed an interesting difference from previous studies in rabbits.

The Chronic Treatment With 5-HT2A Receptor Agonists Affects the Behavior and the BDNF System in Mice.

It is shown for the first time that the chronic activation of the 5-HT2A receptor with agonists has affected the BDNF system almost on all levels-transcription, proBDNF production, TrkB and p75NTR receptors' level.

Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures

Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine

These data indicate that 5-HT2C receptors within the mPFC and the NAC modulate the reinforcing effects of cocaine and provide evidence that5- HT2C receptor agonists could be a possible drug discovery target for the treatment of psychostimulant addiction.

Role of 5-HT(1A)- and 5-HT(2A) receptors for the murine model of the serotonin syndrome.

Role for serotonin 2 A ( 5-HT 2 A ) and 2 C ( 5-HT 2 C ) receptors in experimental absence seizures

5-HT1ARs and 5-HT2CRs negatively control the expression of experimental ASs, indicating that selective agonists at these 5- HT2R subtypes might be potential novel anti-absence drugs.

5-HT2A and mGlu2/3 receptor interactions: on their relevance to cognitive function and psychosis

In-vitro and in-vivo studies documenting the important relationship between 5-HT2A and mGlu2/3 receptors, with relevance to both normal behavioral function and psychosis are focused on.



Evidence that 5-HT2A receptors are not involved in 5-HT-mediated thermoregulation in mice

Direct injection of 5-HT2A receptor agonists into the medial prefrontal cortex produces a head-twitch response in rats.

  • D. WillinsH. Meltzer
  • Biology, Psychology
    The Journal of pharmacology and experimental therapeutics
  • 1997
The findings suggest that the HTR produced by the direct injection of serotonergic agonists into the medial prefrontal cortex is, in part, mediated by the activation of 5-HT2A receptors, which is consistent with other evidence that suggests a functional antagonism between5-HT1A and 5- HT2A receptor activation.

Evidence for functional interactions between 5-HT1A and 5-HT2A receptors in rat thermoregulatory mechanisms.

The present results provide evidence for functional interactions between 5-HT1A and 5- HT2A receptors in temperature regulation in rats, and also suggest an important role for postsynaptic 4-HT2A/C receptors in the mediation of DOI-induced hyperthermia.

Evidence That 5-HT2A Receptors in the Hypothalamic Paraventricular Nucleus Mediate Neuroendocrine Responses to (−)DOI

Data provide the first direct evidence that neuroendocrine responses to a peripheral injection of (−)DOI are predominantly mediated by activation of 5-HT2A receptors in the hypothalamic paraventricular nucleus.

Agonist-directed signaling of the serotonin 2A receptor depends on β-arrestin-2 interactions in vivo

This study suggests that the 5-HT2AR–β-arrestin interaction may be particularly important in receptor function in response to endogenous serotonin levels, which could have major implications in drug development for treating neuropsychiatric disorders such as depression and schizophrenia.

Altered brain serotonin homeostasis and locomotor insensitivity to 3, 4-methylenedioxymethamphetamine ("Ecstasy") in serotonin transporter-deficient mice.

Data suggest that the presence of a functional 5-HTT is essential for brain 5- HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced hyperactivity.

Functional Selectivity of Hallucinogenic Phenethylamine and Phenylisopropylamine Derivatives at Human 5-Hydroxytryptamine (5-HT)2A and 5-HT2C Receptors

The results support the concept of functional selectivity and indicate that subtle changes in ligand structure can result in significant differences in the cellular signaling profile.

Serotonin2 (5-HT2) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibits chlorpromazine- and haloperidol-induced hypothermia in mice.

The results suggest that the chlorpromazine- and haloperidol-induced hypothermia may be mediated by the blockade of the central 5-HT2 receptor.