Biphasic effects of carbamazepine on the dopaminergic system in rat striatum and hippocampus.
To clarify the effects of carbamazepine (CBZ) on dopamine (DA) release and their metabolism, the extracellular and total levels of DA, its metabolites (DOPAC and HVA) and precursor, 3,4-dihydroxyphenylalanine (DOPA) in the striatum and hippocampus were studied. DA re-uptake and DOPA accumulation in the striatum and hippocampus, and monoamine oxidase (MAO) activities were also determined. After acute and chronic administrations of CBZ, the plasma concentration of CBZ associated with therapeutic activity increased the extracellular and total levels of all substances determined, whereas supratherapeutic concentration of CBZ decreased extracellular and total levels of all substances. Neither therapeutic nor supratherapeutic concentrations of CBZ affected MAO-A nor -B activities, nor DA re-uptake. DOPA accumulation caused by NSD1015 was inhibited by therapeutic and supratherapeutic concentrations of CBZ. These results suggest that a therapeutic concentration of CBZ enhances DA turnover, whereas a supratherapeutic concentration of CBZ inhibits DA turnover. These effects of CBZ on dopaminergic systems may be, at least partially, involved in the mechanisms of action of CBZ.
Okada
M
M
Department of Neuropsychiatry, Hirosaki University, Japan. akodamot@cc.hirosaki-u.ac.jp
Hirano
T
T
Mizuno
K
K
Chiba
T
T
Kawata
Y
Y
Kiryu
K
K
Wada
K
K
Tasaki
H
H
Kaneko
S
S
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002220:Carbamazepine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D015102:3,4-Dihydroxyphenylacetic Acid; D002220:Carbamazepine; D004298:Dopamine