Early postnatal clonidine treatment results in altered regional catecholamine utilisation in adult rat brain.
Clonidine is a clinically used antihypertensive which has been suggested to produce physiological changes in children after exposure in utero. The aim of our study was to test the hypothesis that chronic exposure of the developing brain to an alpha 2-adrenergic agonist like clonidine would influence the adult neurochemical setting of central monoamine neurotransmitter systems. Male rat pups were treated from postnatal day 8 to 21 twice daily with saline or with 0.1 mg/kg clonidine. After the last injection on day 21, brain regional catecholamine utilisation was determined using synthesis inhibition with alpha-methyl-p-tyrosine in a subgroup of the pups. The expected decrease in noradrenaline utilisation after clonidine was observed, although statistical significance was not reached in a number of brain regions. Dopamine utilisation was not affected. The other pups were left to reach young adulthood and catecholamine utilisation was measured on day 90. Noradrenaline utilisation on day 90 was significantly decreased in two regions: the medulla-pons and the mesolimbic (dopamine projection) areas. Dopamine utilisation was decreased in the hypothalamus and increased in the amygdala and the cerebellum. These adult neurochemical alterations corroborate previous findings of adult behavioural, physiological and central biochemical alterations in rats exposed to clonidine in early postnatal life.
Netherlands Institute for Brain Research, Amsterdam.
M G
MG
Feenstra
H
H
van Galen
G J
GJ
Boer
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D012701:Serotonin; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine