Modulation of striatal dopamine release by 5-HT2A and 5-HT2C receptor antagonists: [11C]raclopride PET studies in the rat

  title={Modulation of striatal dopamine release by 5-HT2A and 5-HT2C receptor antagonists: [11C]raclopride PET studies in the rat},
  author={Alice Egerton and Rabia Shabir Ahmad and Ella Hirani and Paul M. Grasby},
RationaleAntagonism at serotonin 5-HT2A and 5-HT2C receptors modulates cortical and striatal dopamine (DA) release and may underlie some aspects of the clinical efficacy of ‘atypical’ antipsychotic compounds. However, it is not known whether 5-HT2A/2C receptor-mediated modulation of DA release can be quantified with non-invasive neurochemical imaging, as would be required for investigation of these processes in man.ObjectiveThe objective of the study was to perform a feasibility study in the… 

Effect of 5-HT2A receptor antagonism on levels of D2/3 receptor occupancy and adverse behavioral side-effects induced by haloperidol: a SPECT imaging study in the rat

A partial contribution of a 5-HT 2A R antagonism to the efficacy and side-effect profile of antipsychotic agents is suggested.

Endogenous dopamine release in the human brain as a pharmacodynamic biomarker: evaluation of the new GPR139 agonist TAK-041 with [11C]PHNO PET

The findings suggest that TAK-041 enters the human brain and interacts with GPR139 to affect endogenous dopamine release, and [11C]PHNO PET is a practical method to detect the effects of novel drugs on the brain dopaminergic system in healthy volunteers, in the early stages of drug development.

α2‐Adrenergic drugs modulate the binding of [18F]fallypride to dopamine D2/3 receptors in striatum of living mouse

Findings are consistent with a tonic inhibition of dopamine release by α2 adrenergic receptors, such that α2 blockade increased the competition from endogenous dopamine at D2/3 receptors, thus reducing the [18F]fallypride BPND by about 20%.

Striatal Dopamine Release and Genetic Variation of the Serotonin 2C Receptor in Humans

Findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans.

Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain

Serotonin 2A (5-HT2A) receptors and dopamine D2 receptors are intimately related to the physiology and pathophysiology of neuropsychiatric disorders. A large number of studies have reported the

Sensitivity of [11C]ORM-13070 to increased extracellular noradrenaline in the CNS – a PET study in human subjects

Direct experimental support was gained for the suitability of [11C]ORM-13070 for imaging of brain noradrenergic neurotransmission by revealing significant reductions in B/F ratios in the dorsal striatum, in the brain stem and in several cortical areas.

p-Chloroamphetamine-Enhanced Neostriatal Dopamine Exocytosis in Rats Neonatally Co-lesioned with 6-OHDA and 5,7-DHT: Relevance to Parkinson’s Disease

The overall findings demonstrate that an adulthood serotoninergic nerve lesion enhanced PCA-evoked DA exocytosis in a rodent model of severe PD, while susceptibility to oxidative stress was unchanged.

Receptors in Striatum of Living Mouse

Findings are consistent with a tonic inhibition of dopamine release by a2 adrenergic receptors, such that a2 blockade increased the competition from endogenous dopamine at D2/3 receptors, thus reducing the ( 18 F)fallypride BPND by about 20%.

Presynaptic control of serotonin on striatal dopamine function

A thorough examination of data showing controversial effects induced by striatal 5-HT on dopaminergic activity suggests that the endogenous 5- HT system exerts multiple and subtle influences on DA-mediated behaviors.



Role of Striatal Serotonin2A and Serotonin2C Receptor Subtypes in the Control of In Vivo Dopamine Outflow in the Rat Striatum

Results indicate that striatal 5‐HT2A receptors, probably through activation of DA synthesis, positively modulate DA outflow only under activated conditions, which appears to be both tonic and phasic.

Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies.

The data indicate that MDL 100,907 has a clozapine-like profile of potential antipsychotic activity with low extrapyramidal sid-effect liability.

Modulation of dopamine release by striatal 5‐HT2C receptors

The results suggest that the nigrostriatal system is regulated by 5‐HT2C receptors localized in the dorsal striatum, and that serotonin (5‐HT) modulates striatal and prefrontocortical DA concentrations may lead to improvements in the treatment of diverse syndromes.

Role of serotonin 2A receptors in the D-amphetamine-induced release of dopamine: comparison with previous data on alpha1b-adrenergic receptors.

It is proposed that 5-HT(2A) and alpha1b-adrenergic receptors control a common neural pathway responsible for the release of dopamine in the nucleus accumbens by psychostimulants.

Serotonergic modulation of striatal dopamine measured with positron emission tomography (PET) and in vivo microdialysis

  • S. DeweyG. Smith C. Ashby
  • Biology, Psychology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
These data demonstrate that 5- HT-selective drugs produce changes in striatal dopamine that can be measured noninvasively with PET, and have implications for understanding the therapeutic efficacy of atypical neuroleptics and their utility for treating schizophrenia and affective disorders.

GBR12909 attenuates amphetamine‐induced striatal dopamine release as measured by [11C]raclopride continuous infusion PET scans

The experiments suggest that GBR12909 is an important prototypical medication to test the hypothesis that stimulant‐induced euphoria is mediated by DA and, if the DA hypothesis is correct, a potential treatment agent for cocaine and methamphetamine abuse.