Carbamazepine reduces dopamine-mediated behavior in chronic neuroleptic-treated and untreated rats: implications for treatment of tardive dyskinesia and hyperdopaminergic states.
Chronic treatment with neuroleptic drugs such as haloperidol (HAL) can result in a syndrome of abnormal involuntary movements known as tardive dyskinesia (TD). The authors have obtained evidence that TD in humans is reduced in patients also taking anticonvulsant drugs, primarily carbamazepine (CBZ). To test for a causal role of CBZ in this effect, the authors quantified abnormal movements elicited by dopamine (DA) receptor stimulation in rats (Rattus norvegius) withdrawn from chronic treatment with HAL or CBZ alone or in combination. The expected increased behavioral responsiveness to combined D1/D2 stimulation in rats treated with HAL for 8 weeks was significantly attenuated by chronic CBZ, which also attenuated behavioral responsiveness in otherwise untreated rats. Striatal D2 DA receptor density was elevated in rats treated chronically with HAL but unaffected by CBZ. Striatal D1 DA receptor density was elevated by chronic CBZ but unaffected by HAL. These findings suggest that by reducing DA supersensitivity, CBZ may be useful in treating TD and other hyperdopaminergic states.
LaHoste
Gerald J
GJ
U New Orleans.
Wigal
Tim
T
King
Bryan H
BH
Schuck
Sabrina E B
SEB
Crinella
Francis M
FM
Swanson
James M
JM
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D002220:Carbamazepine; D006220:Haloperidol; D004298:Dopamine