title: Histamine H3 receptor agonist- and antagonist-evoked vacuous chewing movements in 6-OHDA-lesioned rats occurs in an absence of change in microdialysate dopamine levels.
abstract: 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(1)/D(5) receptor agonist, produces robust stereotyped and locomotor activities. The gradual induction of dopamine D(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 Parkinson's disease patients. The object of the present study was to determine the possible influence of the histaminergic system on dopamine D(1) agonist-induced activities. We found that neither imetit (5.0 mg/kg i.p.), a histamine H(3) receptor agonist, nor thioperamide (5.0 mg/kg i.p.), a histamine H(3) receptor antagonist/inverse agonist, altered the numbers of vacuous chewing movements in non-primed-lesioned rats. However, in dopamine D(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(1)/D(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.
authors.affiliation: Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland. pnowak@slam.katowice.pl
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.forename: Joanna
authors.initials: J
authors.lastname: Dabrowska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bortel
authors.forename: Izabela
authors.initials: I
authors.lastname: Biedka
authors.forename: Grazyna
authors.initials: G
authors.lastname: Szczerbak
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Słomian
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015314:Dialysis Solutions / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000502:physiology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D015314:Dialysis Solutions; D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; D018100:Receptors, Histamine H3; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C077430:imetit; D016627:Oxidopamine; D013890:Thiourea; C052075:thioperamide; D004298:Dopamine