Neonatal administration of a GABA-T inhibitor alters central GABAA receptor mechanisms and alcohol drinking in adult rats.
Long-term effects of chronic treatment with a GABA-T (GABA-transaminase) inhibitor, ethanolamine O-sulphate (EOS) (200 mg/kg/day for the postnatal days 3-21) on the binding parameters of GABAA receptors, hypothalamic monoamines and subsequent behavior were studied in Wistar rats. At the age of 1 month, EOS-treated rats showed reduced activity in the open-field and, at the age of 4 months, their voluntary alcohol consumption was increased. No changes were seen in Porsolt's swim test or in the plus-maze test. Weight gain was significantly retarded in EOS-treated rats. Maximal stimulation of [3H] flunitrazepam binding by GABA was decreased in the cerebral cortex and the EC50-value for the GABA stimulation increased in the hippocampus in the EOS rats at the age of 4 months. EOS treatment did not alter the cerebellar diazepam sensitive and insensitive binding components of the imidazobenzodiazepine [3H]Ro 15-4513. No changes were observed in the hypothalamic monoamine concentrations. The results are in agreement with the idea that GABA-T inhibitor treatment permanently alters GABAA mechanisms. Moreover, altering the CNS GABA level during development increases adult alcohol intake in rat.
Táira
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University of Helsinki, Department of Physiology, Helsinki, Finland.
Porkka-Heiskanen
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Korpi
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D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005445:Flunitrazepam / Q000493:pharmacokinetics; D006380:Helplessness, Learned; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D015430:Weight Gain / Q000187:drug effects
D015306:Biogenic Monoamines; D004983:Ethanolamines; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C020619:ethanolamine O-sulfate; D000612:4-Aminobutyrate Transaminase