Neuroimaging and 5-HT2C receptor polymorphism: a HMPAO-SPECT study in healthy male probands using mCPP-challenge of the 5-HT2C receptor.
BACKGROUND
The human 5-HT (2C) receptor gene has been localized on the X chromosome and is expressed in two genetic variants. Whereas previous investigations have suggested that the 5-HT (2C) receptor gene polymorphism is critically involved in the pathogenesis of affective and eating disorders, as yet the functional consequences being associated with the rare serine variant of the 5-HT (2C) receptor in humans are unclear.


METHODS
We explored by HMPAO-SPECT if a challenge with the serotonin agonist mCPP, that interacts mainly with the 5-HT (2C) receptor, provokes different patterns of regional cerebral bloodflow (rCBF) as a function of the genetic variant of the receptor. Thus we studied its action in 16 healthy male volunteers carrying the common 5-HT (2C)-cys-23 receptor gene and 16 healthy male volunteers carrying the less frequent 5-HT (2C)-ser-23 receptor gene.


RESULTS
We found significant differences in rCBF between the two genotypes after mCPP infusion compared to placebo: In the cysteine group rCBF was increased in the left medial prefrontal cortex and decreased in the left anterior cingulate and right medio-temporal cortex, whereas the serine group showed an increase of rCBF in the left medio- and superior-temporal cortex and in cerebellum and a reduced rCBF in the right medial prefrontal cortex. In addition, there was a significant disordinal interaction of the genotype factors and challenge with an increase of rCBF in the serine group and a decrease in the cysteine group in the left motor cortex and calcarine cortex. Additionally, a decrease of rCBF in the serine-group and a simultaneous increase in the cysteine group was found in the right anterior and the left posterior cingulate cortex.


CONCLUSIONS
These findings suggest that differences in the 5-HT (2C) receptor gene polymorphism has functional consequences due to a different responsiveness of the expressed 5-HT (2C) receptor variants.
Kühn
K-U
KU
Department of Psychiatry, University Clinic for Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. k.u.keuhn@uni-bonn.de
Joe
A Y
AY
Meyer
K
K
Reichmann
K
K
Maier
W
W
Rao
M L
ML
Reinhardt
M J
MJ
Biersack
H-J
HJ
Quednow
B B
BB
D000328:Adult; D001007:Anxiety / Q000188:drug therapy; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D003545:Cysteine / Q000378:metabolism; D003710:Demography; D004311:Double-Blind Method; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists; D019690:Technetium Tc 99m Exametazime; D012694:Serine; D003545:Cysteine; C015068:1-(3-chlorophenyl)piperazine