Histamine H sub(3) receptor agonist- and antagonist-evoked vacuous chewing movements in 6-OHDA-lesioned rats occurs in an absence of change in microdialysate dopamine levels

• Published in: European journal of pharmacology 2006-12, Vol.552 (1-3), p.46-54
• Main Authors: Nowak, Przemyslaw, Dabrowska, Joanna, Bortel, Aleksandra, Biedka, Izabela, Szczerbak, Grayna, Slomian, Grzegorz, Kostrzewa, Richard M, Brus, Ryszard
• Format: Article
• Language: English
• ISSN: 0014-2999
• DOI: 10.1016/j.ejphar.2006.08.092

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 D sub(1)/D sub(5) receptor agonist, produces robust stereotyped and locomotor activities. The gradual induction of dopamine D sub(1) 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 Parkinsons disease patients. The object of the present study was to determine the possible influence of the histaminergic system on dopamine D sub(1) agonist-induced activities. We found that neither imetit (5.0 mg/kg i.p.), a histamine H sub(3) receptor agonist, nor thioperamide (5.0 mg/kg i.p.), a histamine H sub(3) receptor antagonist/inverse agonist, altered the numbers of vacuous chewing movements in non-primed-lesioned rats. However, in dopamine D sub(1) 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 D sub(1)/D sub(5) 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.