Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome.
BACKGROUND
Chronic fatigue syndrome (CFS) has been associated with increased prolactin (PRL) responses to the serotonin (5-HT) releasing agent fenfluramine. It is not known whether this abnormality is due to increased 5-HT release or heightened sensitivity of post-synaptic 5-HT receptors.


METHODS
We measured the increase in plasma PRL produced by the directly acting 5-HT receptor agonist, m-chlorophenylpiperazine (mCPP), in patients with CFS and healthy controls. We also compared the ability of mCPP to lower slow wave sleep (SWS) in the sleep polysomnogram of both subject groups. Finally, we measured plasma amino-acid levels to determine whether tryptophan availability differed between CFS subjects and controls.


RESULTS
mCPP elevated plasma PRL equivalently in patients with CFS and controls. Similarly, the decrease in SWS produced by mCPP did not differ between the two subject groups. Plasma-free tryptophan was significantly decreased in CFS.


CONCLUSIONS
The sensitivity of post-synaptic 5-HT2c receptors is not increased in patients with CFS. This suggests that the increased PRL response to fenfluramine in CFS is due to elevated activity of pre-synaptic 5-HT neurones. This change is unlikely to be due to increased peripheral availability of tryptophan.
Vassallo
C M
CM
University Department of Psychiatry, Warneford Hospital, Oxford.
Feldman
E
E
Peto
T
T
Castell
L
L
Sharpley
A L
AL
Cowen
P J
PJ
D000328:Adult; D015673:Fatigue Syndrome, Chronic / Q000503:physiopathology*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013570:Synaptic Membranes / Q000502:physiology; D014364:Tryptophan / Q000097:blood / Q000378:metabolism*
D005277:Fenfluramine; D010879:Piperazines; D011388:Prolactin; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; C015068:1-(3-chlorophenyl)piperazine