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Histaminergic Activity in a Rodent Model of Parkinson’s Disease
- Source :
- Neurotoxicity Research. 15:246-251
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- Rats lesioned shortly after birth with 6-OHDA have been proposed to be a near-ideal model of severe Parkinson's disease, because of non-lethality of the procedure, near-total destruction of nigrostriatal dopaminergic fibers, and near-total dopamine (DA) denervation of striatum. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. Therefore, the aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats. At 3 days after birth, Wistar rats were pretreated with desipramine (20.0 mg/kg ip) 1 h before bilateral icv administration of the catecholaminergic neurotoxin 6-OHDA (67 microg base, on each side) or saline-ascorbic acid (0.1%) vehicle (control). At 8 weeks levels of DA and its metabolites L: -3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) were estimated in the striatum and frontal cortex by HPCL/ED technique. In the hypothalamus, hippocampus, frontal cortex, and medulla oblongata, the level of histamine was analyzed by immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped-activity) were additionally made on control and 6-OHDA neonatally lesioned rats. Effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists (e.g., S(+)chlorpheniramine, H(1); cimetidine, H(2); thioperamide, H(3) agonist) were determined. We confirmed that 6-OHDA significantly reduced contents of DA and its metabolites in the brain in adulthood. Histamine content was significantly increased in the hypothalamus, hipocampus, and medulla oblongata. Moreover, in 6-OHDA-lesioned rats behavioral response was altered mainly by thioperamide (H(3) antagonist). These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that histaminergic neurons exert a modulating role in Parkinsonian 6-OHDA-lesioned rats.
- Subjects :
- Male
medicine.medical_specialty
Apomorphine
Dopamine
Histamine Antagonists
Striatum
Toxicology
chemistry.chemical_compound
Adrenergic Agents
Internal medicine
Animals
Medicine
Rats, Wistar
Oxidopamine
Thioperamide
Dose-Response Relationship, Drug
business.industry
General Neuroscience
Dopaminergic
Histaminergic
Brain
Parkinson Disease
Rats
Disease Models, Animal
Endocrinology
Animals, Newborn
nervous system
chemistry
Dopamine Agonists
Exploratory Behavior
Mouth Abnormalities
Histamine H3 receptor
business
Locomotion
Histamine
medicine.drug
Subjects
Details
- ISSN :
- 14763524 and 10298428
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Neurotoxicity Research
- Accession number :
- edsair.doi.dedup.....2cb5b5d09f0ff28101d144f9e38a8726