Carbamazepine suppresses methamphetamine-induced Fos expression in a regionally specific manner in the rat brain. Possible neural substrates responsible for antimanic effects of mood stabilizers.
Carbamazepine (CBZ) has been widely used for treatment of manic states. Because amphetamine produces effects in humans similar to those of idiopathic mania, acute methamphetamine administration could serve as a model of this condition. To elucidate the neurobiological substrates responsible for the antimanic effects of carbamazepine, this study investigated the effects of chronic carbamazepine administration on regional Fos protein expression induced by a single dose of methamphetamine (2mg/kg). Chronic treatment with CBZ (0.25% in food for 7 days, followed by 0.5% for 7 days; final mean serum carbamazepine concentration: 4.09 +/- 0.34 microg/ml) significantly attenuated the number of Fos-like immunoreactivity-positive nuclei induced by methamphetamine administration in the core of the nucleus accumbens and the caudate/putamen. The results indicate these brain regions are involved in the antimanic effects of carbamazepine.
Lee
Y
Y
Department of Neuropsychiatry, Okayama University Medical School, Okayama, Japan.
Hamamura
T
T
Ohashi
K
K
Miki
M
M
Fujiwara
Y
Y
Kuroda
S
S
D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D018692:Antimanic Agents / Q000097:blood / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D002220:Carbamazepine / Q000097:blood / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D004334:Drug Administration Schedule; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D017072:Neostriatum / Q000187:drug effects / Q000503:physiopathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats
D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D016760:Proto-Oncogene Proteins c-fos; D002220:Carbamazepine; D008694:Methamphetamine