title: Presynaptic 5-HT1A is related to 5-HTT receptor density in the human brain.
abstract: 5-Hydroxytryptamine (5-HT or serotonin) is an important neurotransmitter for a number of brain functions and widely distributed throughout the brain. Physiological and pharmacological relationship between 5-HT1A receptors and serotonin transporter (5-HTT) in the regulation of 5-HT neurotransmission has now been documented. A relationship between 5-HT1A receptors and 5-HTT is also suggested by the pathophysiology of depression and the mechanism of action of antidepressants. We have scanned 42 healthy adults with both [11C] WAY-100635 and [11C] DASB to investigate the anatomical co-distribution of multiple serotonergic markers. We hypothesized that lower 5-HTT densities in the dorsal raphe nucleus (DRN) and limbic regions will be accompanied by lower 5-HT1A receptor density in the same regions, contributing to the 5-HT1A receptor desensitization. In addition, variations in DRN 5-HT1A receptor density can theoretically influence the density and/or function of other serotonin receptor subtypes and the 5-HTT consequent to changes in serotonergic tone. In a comparatively large sample of volunteers, we have shown that the relationship between 5-HT1A and 5-HTT PET indices was complex. We were unable to demonstrate robust, intra-regional relationships between 5-HT1A and 5-HTT densities. Inter-regionally, DRN 5-HT1A receptors were related to cortical (temporal and frontal regions) and paralimbic (insula), but not limbic 5-HTT. This latter finding may reflect differences in 5-HT tone between individuals, and highlights probable substrates sensitive to variations in DRN 5-HT function.
authors.affiliation: PET Methodology, MRC-Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, London, UK. subrata.bose@imperial.ac.uk
authors.forename: Subrata K
authors.initials: SK
authors.lastname: Bose
authors.forename: Mitul A
authors.initials: MA
authors.lastname: Mehta
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Selvaraj
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.forename: Rainer
authors.initials: R
authors.lastname: Hinz
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Paul M
authors.initials: PM
authors.lastname: Grasby
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Venkatesha
authors.initials: V
authors.lastname: Murthy
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods; D017729:Presynaptic Terminals / Q000000981:diagnostic imaging / Q000378:metabolism*; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*
chemical_list: D010879:Piperazines; D011725:Pyridines; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide