High resolution micro-SPECT scanning in rats using 125I beta-CIT: effects of chronic treatment with carbamazepine.
OBJECTIVE
Carbamazepine (CBZ) is a first-line antiepileptic agent with mood-stabilizing effects in bipolar disorder. It has been reported to influence extracellular concentrations of serotonin and dopamine, suggesting an interaction with monoamine transporters. We have investigated this effect using in vivo single photon emission computed tomography (SPECT) in rats.


METHODS
Adult male rats received 3 mg/kg/h CBZ via mini-osmotic pump. After 14 days continuous treatment, animals underwent two consecutive SPECT scans, using 125I beta-CIT as a radiotracer to label serotonin transporter (SERT) and dopamine transporter (DAT) sites in the brain. Pharmacologic distinction was enabled by 125I beta-CIT SPECT imaging in rats acutely exposed to the serotonin and dopamine transporter inhibitors, fluoxetine and GBR12909. The interaction between CBZ and 125I beta-CIT binding to SERT and DAT was investigated using in vitro autoradiography.


RESULTS
Carbamazepine (10 microm) did not affect binding of 125I beta-CIT to isolated rat brain slices, thereby excluding a direct effect on ligand binding to SERT and DAT. SPECT studies with fluoxetine and GBR12909 highlighted SERT binding in thalamus, hippocampus, centromedial nuclei, and occipital cortex, and DAT binding in the caudate. Prolonged treatment with CBZ failed to influence 125I beta-CIT binding to either SERT or DAT in any of the brain regions examined.


CONCLUSIONS
This study employed the novel technique of small animal SPECT imaging to investigate the effects of CBZ on monoamine transporters in rat brain. Following prolonged treatment, the drug was without effect on SERT or DAT availability. The mechanism by which CBZ exerts its mood stabilizing effects remains elusive.
Cain
Stuart M
SM
Epilepsy Unit, Division of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Ruest
Torsten
T
Pimlott
Sally
S
Patterson
Jim
J
Duncan
Rod
R
Dewar
Debbie
D
Sills
Graeme J
GJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001345:Autoradiography / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D001931:Brain Mapping; D002220:Carbamazepine / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D019275:Radiopharmaceuticals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D000927:Anticonvulsants; D018765:Dopamine Uptake Inhibitors; D007457:Iodine Radioisotopes; D010879:Piperazines; D019275:Radiopharmaceuticals; D002220:Carbamazepine; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; C043425:vanoxerine; D003042:Cocaine