Pharmacological model of catecholamine depletion in the hypothalamus of fetal and neonatal rats and its application.
1. The present study aimed to develop a pharmacological model of catecholamine (CA) depletion in the hypothalamus during the period of its morphofunctional development, i.e. in fetal and neonatal rats of both sexes. 2. In the first series of experiments, pregnant females and, hence, fetuses were systemically treated daily from the embryonic day (E) 13 to E20 with the inhibitor of the CA synthesis alpha-methyl-m-tyrosine. The CA concentrations were subsequently measured in the fetal hypothalamus at E21 by high performance liquid chromatography with electrochemical detection (HPLC-ED). In the second series of experiments, neonatal rats were injected with neurotoxin, 6-hydroxydopamine and/or alpha-methyl-m-tyrosine daily from the 2nd postnatal day (P2) to P10. 3. The HPLC-ED assay of hypothalamic catecholamines (CA's) at E21 and P11 showed that both in fetuses and neonates, alpha-methyl-m-tyrosine caused more than 50% depletion of hypothalamic noradrenaline and adrenaline, while the dopamine (DA) level remained unchanged. The combined treatment of neonatal rats with alpha-methyl-m-tyrosine and 6-hydroxydopamine resulted additionally in a 25% decreased level of DA. 4. The influence of CA deficiency on the developing hypothalamic CA system was further evaluated by measuring [3H]DA uptake by nervous tissue in vitro. 5. The CA deficiency caused a 50% drop of [3H]DA uptake by the hypothalamic tissue in treated fetuses suggesting a stimulating effect of CA's on the early development of the CA system. In pharmacologically treated neonatal rats [3H]DA uptake remained at the control level showing no influence of the CA deficiency on the developing CA system after birth. 6. The usefulness of the proposed pharmacological model for studying of CA influence on differentiating hypothalamic target neurons is discussed.
Bernabe
J
J
Laboratory of Physiology of Reproduction, Institute of Neurosciences CNRS URA 1488, University P. and M. Curie, Paris, France.
Proshlyakova
E
E
Sapronova
A
A
Trembleau
A
A
Calas
A
A
Ugrumov
M
M
D000818:Animals; D000831:Animals, Newborn; D002395:Catecholamines / Q000172:deficiency*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000172:deficiency; D004357:Drug Synergism; D004837:Epinephrine / Q000172:deficiency; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D009638:Norepinephrine / Q000172:deficiency; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002395:Catecholamines; D008781:Methyltyrosines; D009498:Neurotoxins; D016627:Oxidopamine; C031476:alpha-methyl-m-tyrosine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine