H3 Receptor Agonist- and Antagonist-Evoked Vacuous Chewing Movements in 6-OHDA-Lesioned Rats Occurs in an Absence of Change in Microdialysate Dopamine Levels
Document Type
Article
Publication Date
12-15-2006
Description
In rats lesioned neonatally with 6-hydroxydopamine (6-OHDA), repeated treatment with SKF 38393 (1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol), a dopamine D1/D5 receptor agonist, produces robust stereotyped and locomotor activities. The gradual induction of dopamine D1 receptor supersensitivity is known as a priming phenomenon, and this process is thought to underlie not only the appearance of vacuous chewing movements in humans with tardive dyskinesia, but also the onset of motor dyskinesias in l-dihydroxyphenylalanine (l-DOPA)-treated Parkinson's disease patients. The object of the present study was to determine the possible influence of the histaminergic system on dopamine D1 agonist-induced activities. We found that neither imetit (5.0 mg/kg i.p.), a histamine H3 receptor agonist, nor thioperamide (5.0 mg/kg i.p.), a histamine H3 receptor antagonist/inverse agonist, altered the numbers of vacuous chewing movements in non-primed-lesioned rats. However, in dopamine D1 agonist-primed rats, thioperamide alone produced a vacuous chewing movements response (i.e., P < 0.05 vs SKF 38393, 1.0 mg/kg i.p.), but did not modify the SKF 38393 effect. Notably, both imetit and thioperamide-induced catalepsy in both non-primed and primed 6-OHDA-lesioned rats, comparable in magnitude to the effect of the dopamine D1/D5 receptor antagonist SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0.5 mg/kg i.p.). Furthermore, in primed animals both imetit and thioperamide intensified SCH 23390-evoked catalepsy. In vivo microdialysis established that neither imetit nor thioperamide altered extraneuronal levels of dopamine and its metabolites in the striatum of 6-OHDA-lesioned rats. On the basis of the present study, we believe that histaminergic systems may augment dyskinesias induced by dopamine receptor agonists, independent of direct actions on dopaminergic neurons.
Citation Information
Nowak, Przemysław; Dabrowska, Joanna; Bortel, Aleksandra; Biedka, Izabela; Szczerbak, Grazyna; Słomian, Grzegorz; Kostrzewa, Richard M.; and Brus, Ryszard. 2006. H3 Receptor Agonist- and Antagonist-Evoked Vacuous Chewing Movements in 6-OHDA-Lesioned Rats Occurs in an Absence of Change in Microdialysate Dopamine Levels. European Journal of Pharmacology. Vol.552(1-3). 46-54. https://doi.org/10.1016/j.ejphar.2006.08.092 PMID: 17055481 ISSN: 0014-2999