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)....

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Published in:Experimental and clinical psychopharmacology 2000-02, Vol.8 (1), p.125-132
Main Authors: LaHoste, Gerald J, Wigal, Tim, King, Bryan H, Schuck, Sabrina E. B, Crinella, Francis M, Swanson, James M
Format: Article
Language:English
Subjects:
Animal
Animals
Anticonvulsants - pharmacology
Antipsychotic Agents - pharmacology
Behavior
Behavior, Animal - drug effects
Carbamazepine
Carbamazepine - pharmacology
Dopamine
Dopamine - biosynthesis
Dopamine - physiology
Dopamine Antagonists - pharmacology
Dyskinesia, Drug-Induced - drug therapy
Female
Haloperidol - pharmacology
Neostriatum - drug effects
Neostriatum - metabolism
Neuroleptic Drugs
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 - drug effects
Receptors, Dopamine D2 - drug effects
Stereotyped Behavior - drug effects
Tardive Dyskinesia
Up-Regulation - drug effects
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Summary: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the authors quantified abnormal movements elicited by dopamine (DA) receptor stimulation in rats ( Rattus norvegius ) withdrawn from chronic treatment with HAL or CBZ alone or in combination.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.
ISSN:1064-1297
1936-2293
DOI:10.1037/1064-1297.8.1.125