Presynaptic 5-ht1a is related to 5-HTT receptor density in the human brain

Subrata K. Bose, Mitul A. Mehta, Sudhakar Selvaraj, Oliver D. Howes, Rainer Hinz, Eugenii A. Rabiner, Paul M. Grasby, Federico E. Turkheimer, Venkatesha Murthy

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2258-2265
Number of pages8
JournalNeuropsychopharmacology
Volume36
Issue number11
DOIs
StatePublished - Oct 2011

Keywords

  • 5-HT1A
  • 5-HTT
  • PET
  • antidepressants
  • drug discovery
  • serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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