title: The effect of a 5-HT1A receptor agonist on striatal dopamine release.
abstract: 5-HT1A receptor agonists consistently reduce neuroleptic induced catalepsy in rats. A serotonin-dopamine interaction has been proposed to underlie this effect. Specifically, 5-HT1A receptor agonists may reduce the activity of serotonergic projections that inhibit dopaminergic nigrostriatal neurones, therefore increasing dorsal striatal dopamine levels and partially overcoming the neuroleptic blockade of D2 receptors. We tested the hypothesis that 5-HT1A receptor agonists increase striatal dopamine release in man using PET scanning with the selective D2 receptor radioligand [11C]raclopride, which is sensitive to endogenous dopamine levels. Six healthy volunteers received two PET scans, one after placebo, the other after 1 mg flesinoxan, a selective 5-HT1A receptor agonist. Binding potential values for striatal subdivisions were determined using a simplified reference tissue model. We did not find any difference in striatal [11C]raclopride binding between conditions, even though flesinoxan lead to typical 5-HT1A receptor agonist side effects and produced elevation of growth hormone in five of the six subjects. Our results suggest that the anticataleptic effect of 5-HT1A receptor agonists is not mediated by striatal dopamine release, and indicates a need for further research with other suitable 5-HT1A receptor agonists.
authors.affiliation: Cyclotron Unit, CSC, The Hammersmith Hospital, Imperial College London, London W12 0NN, United Kingdom. rabantick@doctors.org.uk
authors.forename: R Alexander
authors.initials: RA
authors.lastname: Bantick
authors.forename: Michiel H
authors.initials: MH
authors.lastname: De Vries
authors.forename: Paul M
authors.initials: PM
authors.lastname: Grasby
mesh_terms: D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes / Q000378:metabolism; D002375:Catalepsy / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000097:blood / Q000494:pharmacology; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000378:metabolism / Q000493:pharmacokinetics; D011869:Radioligand Assay; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D010879:Piperazines; D017448:Receptors, Dopamine D2; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; C056895:flesinoxan; D020891:Raclopride; D013006:Growth Hormone; D004298:Dopamine