Persistent oral dyskinesias in haloperidol-withdrawn neonatal 6-hydroxydopamine-lesioned rats.
Because chronic haloperidol-treated rats demonstrate an increased incidence of spontaneous oral activity, while neonatal 6-hydroxydopamine-lesioned rats demonstrate an increased incidence of dopamine agonist-induced oral activity, we studied the influence of haloperidol in 6-hydroxydopamine-lesioned rats. At 3 days after birth rats received 6-hydroxydopamine hydrobromide (200 micrograms intracerebroventricularly; desipramine pretreatment, 20 mg/kg i.p., 1 h) or vehicle. Two months later haloperidol (1.5 mg/kg per day x 2 days per week, for 4 weeks; then 1.5 mg/kg per day, every day for 10 months) was added to the drinking water. After 15 weeks the level of spontaneous oral activity was stable. At 11 months there were 35.8 +/- 4.9 vs. 18.4 +/- 2.1 oral movements in 6-hydroxydopamine-lesioned vs. intact rats receiving haloperidol. This effect persisted unabated in lesioned rats for 4 months after haloperidol withdrawal. This stable high frequency of oral dyskinesias is an advantage for studying putative therapeutic drugs for tardive dyskinesia.
Huang
N Y
NY
Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City 37614-0577.
Kostrzewa
R M
RM
D000818:Animals; D000831:Animals, Newborn; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D006220:Haloperidol / Q000633:toxicity*; D009055:Mouth / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000502:physiology*; D013997:Time Factors
D011954:Receptors, Dopamine; D016627:Oxidopamine; D006220:Haloperidol