Acute and chronic tryptophan depletion differentially regulate central 5-HT1A and 5-HT 2A receptor binding in the rat.
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.
Cahir
Marie
M
Division of Psychiatry and Neuroscience, Queen's University Belfast, Whitla, 97 Lisburn Road, Northern Ireland, UK. m.cahir@qub.ac.uk
Ardis
Tara
T
Reynolds
Gavin P
GP
Cooper
Stephen J
SJ
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*
D017660:Autoreceptors; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D014364:Tryptophan