title: Acute and chronic tryptophan depletion differentially regulate central 5-HT1A and 5-HT 2A receptor binding in the rat.
abstract: BACKGROUND
  Tryptophan depletion is used to reduce central serotonergic function and to investigate its role in psychiatric illness. Despite widespread clinical use, its effects on serotonin (5-HT) receptors have not been well characterized.
  
  
  OBJECTIVE
  The aim of this study was to examine the effect of acute (ATD) and chronic tryptophan depletion (CTD) on free-plasma tryptophan (TRP), central TRP and 5-HT and brain 5-HT(1A) and 5-HT(2A) receptor binding in the rat.
  
  
  METHODS
  TRP and 5-HT were measured by high-performance liquid chromatography and receptor levels determined by homogenate radioligand binding and in-vitro receptor autoradiography.
  
  
  RESULTS
  Free-plasma TRP, central TRP and central 5-HT levels were significantly and similarly reduced by ATD and 1- and 3-week CTD compared to controls. ATD significantly reduced 5-HT(1A) binding in the dorsal raphe (14%) but did not significantly alter postsynaptic 5-HT(1A) binding (frontal cortex, remaining cortex and hippocampus) or 5-HT(2A) binding (cortex and striatum). One-week CTD did not significantly alter cortical 5-HT(2A) binding or postsynaptic 5-HT(1A) binding. Furthermore, 3-week CTD did not significantly alter 5-HT(1A) binding but significantly increased cortical 5-HT(2A) binding without affecting striatal or hippocampal levels. In the CTD 1 and 3-week groups, rat body weight was significantly decreased as compared to controls. However, weight loss was not a confounding factor for decreased cortical 5-HT(2A)-receptor binding.
  
  
  CONCLUSIONS
  ATD-induced reduction in somatodendritic 5-HT(1A) autoreceptor binding may represent an intrinsic 'homeostatic response' reducing serotonergic feedback in dorsal raphe projection areas. In contrast, the increase in 5-HT(2A) receptor after CTD may be a compensatory response to a long-term reduction in 5-HT.
authors.affiliation: Division of Psychiatry and Neuroscience, Queen's University Belfast, Whitla, 97 Lisburn Road, Northern Ireland, UK. m.cahir@qub.ac.uk
authors.forename: Marie
authors.initials: M
authors.lastname: Cahir
authors.forename: Tara
authors.initials: T
authors.lastname: Ardis
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Reynolds
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001345:Autoradiography; D017660:Autoreceptors / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D025461:Feedback, Physiological; D008297:Male; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014364:Tryptophan / Q000097:blood / Q000172:deficiency*
chemical_list: D017660:Autoreceptors; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D014364:Tryptophan