Acute haloperidol administration induces depolarization block of nigral dopamine neurons in rats after partial dopamine lesions
Abstract
The effects of the antipsychotic drug haloperidol (HAL) on the electrophysiological activity of dopamine (DA)-containing cells in the substantia nigra was assessed in rats 6 weeks after partial 6-hydroxydopamine (6-OHDA)-induced lesions of the nigrostriatal DA pathway. Depleting 75% or more of striatal DA altered the response of DA neurons to acute HAL administration. Whereas acute HAL administration generally accelerates DA neuron firing in control rats, similar HAL doses given to lesioned rats not only increased firing rate but induced depolarization block of DA neuron spike generation similar to that resulting from chronic neuroleptic administration. In contrast, acute administration of doses of HAL up to lethal levels typically could not induce depolarization block of DA neurons in non-lesioned rats. This preparation thus could be an effective model for investigating the exacerbation of behavioral deficits produced by an increased demand placed upon a compromised DA system, as may occur in Parkinson's disease or with antipsychotic drug treatment.
References
Comparison of the effects of chronic haloperidol treatment on A9 and A10 dopamine neurons in the rat
Citations
Physiology of the normal and dopamine-depleted basal ganglia: insights into levodopa pharmacotherapy
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