Ontogenetic serotoninergic lesioning alters histaminergic activity in rats in adulthood.
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 lesioned as neonates with the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At 3 days after birth Wistar rats were pretreated with desipramine (20 mg/kg ip) before bilateral icv administration of 5,7-DHT (37.5 μg base on each side) or saline-ascorbic (0.1%) vehicle (control). At 10 week levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were determined in frontal cortex, striatum, and hippocampus by an HPLC/ED technique. In the hypothalamus, frontal cortex, hippocampus and medulla oblongata, the level of histamine was analyzed by an immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped activity) were performed, and effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists S(+)chlorpheniramine (H(1)), cimetidine (H(2)), and thioperamide (H(3)) were determined. We confirmed that 5,7-DHT profoundly reduced contents of 5-HT and 5-HIAA in the brain in adulthood. Histamine content was also reduced in all examined brain regions. Moreover, in 5,7-DHT-lesioned rats the locomotor and oral activity responses to thioperamide were altered, and apomorphine-induced stereotype was intensified. From the above, we conclude that an intact central serotoninergic system modulates histamine H(3) receptor antagonist effects on the dopaminergic neurons in rats.
Jośko
Jadwiga
J
Department of Environmental Medicine and Epidemiology, Medical University of Silesia, 41-808, Zabrze, Poland.
Drab
Jacek
J
Jochem
Jerzy
J
Nowak
Przemysław
P
Szkilnik
Ryszard
R
Korossy-Mruk
Eva
E
Boroń
Dariusz
D
Kostrzewa
Richard M
RM
Brus
Halina
H
Brus
Ryszard
R
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003891:Desipramine / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006632:Histamine / Q000378:metabolism*; D006633:Histamine Antagonists / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth / Q000187:drug effects / Q000502:physiology; D009068:Movement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000633:toxicity; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006632:Histamine; D001058:Apomorphine; D003891:Desipramine