title: Persistent spontaneous oral dyskinesias in haloperidol-withdrawn rats neonatally lesioned with 6-hydroxydopamine: absence of an association with the Bmax for [3H]raclopride binding to neostriatal homogenates.
abstract: To investigate the influence of dopamine (DA) nerves on haloperidol (HAL)-induced oral dyskinesias, rats were first injected at 3 days after birth with 6-hydroxydopamine HBr (200 micrograms i.c.v., salt form; 6-OHDA) or vehicle, after desipramine HCl (20 mg/kg i.p., 1 hr) pretreatment. Two months later HAL (1.5 mg/kg/day, 2 days a week for 4 weeks, then daily for 10 months) was added to the drinking water of half the rats. Numbers of vacuous chewing movements, recorded in 1-min increments every 10 min for 1 hr, increased from < 5 to about 17 oral movements per session in intact rats, 14 weeks after instituting HAL (P < .01 vs. intact rats drinking tap water). In HAL-treated 6-OHDA-lesioned rats, oral activity increased to > 30 oral movements per session (P < .01 vs. HAL-treated intact rats). These levels of oral activity persisted in intact and 6-OHDA-lesioned rats as long as HAL was administered. After 11 months of HAL treatment, but 8 or 9 days after HAL withdrawal, DA was found to be reduced 97%, whereas serotonin was increased 29% in the striatum of 6-OHDA-lesioned rats. In HAL-treated intact and lesioned rats the Bmax for DA D2 binding sites was elevated about 70%. With reverse transcription polymerase chain reaction, the mRNA level for DA D2L but not D2S receptors was also found to be elevated about 70%. In a fraction of 6-OHDA-lesioned rats that were observed for 8 months after HAL withdrawal, oral activity persisted without decrement and was not accompanied by a change in the Bmax or mRNA level for DA D2 receptors. These findings demonstrate that in rats largely DA-denervated as neonates, long-term HAL treatment produces an unusually high number of oral movements that persists for 8 months after HAL withdrawal and is not accompanied by an increase in DA D2 receptor expression.
authors.affiliation: Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, USA.
authors.forename: N Y
authors.initials: NY
authors.lastname: Huang
authors.forename: R M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: K W
authors.initials: KW
authors.lastname: Perry
authors.forename: R W
authors.initials: RW
authors.lastname: Fuller
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015306:Biogenic Monoamines / Q000032:analysis / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D009059:Mouth Diseases / Q000139:chemically induced*; D016627:Oxidopamine; D012333:RNA, Messenger / Q000032:analysis; D020891:Raclopride; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics; D012457:Salicylamides / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D015306:Biogenic Monoamines; D018492:Dopamine Antagonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012457:Salicylamides; D020891:Raclopride; D016627:Oxidopamine; D004298:Dopamine