Early postnatal treatment with muscimol transiently alters brain GABAA receptors and open-field behavior in rat.
The long-term effects of treatment with muscimol, a GABAA agonist, and with ethanol, also shown to have a GABAergic profile of action, on subsequent behavior and on the binding parameters of GABAA receptors were studied in Wistar rats. Rats were given two daily injections of muscimol (0.1 mg/kg M1 group of 0.2 mg/kg M2 group) or ethanol (1.5 g/kg) between the 1st and 21st postnatal days, with saline-treated animals serving as controls. At the age of one month, the activity of the M2 rats was decreased in the open-field arena. At the age of four months, ethanol-treated rats consumed less 10% ethanol solution in a free choice situation. No changes were seen in the elevated plus-maze test. Maximal GABA stimulation of [3H]flunitrazepam binding was decreased in the cerebellum and hippocampus in M2 rats at the age of one month but not four months. A significant positive correlation was found in all rats between maximal GABA-stimulated [3H]flunitrazepam binding in the cerebellum and ambulation in the open-field arena at the age of one month. Ethanol intake correlated negatively with maximal GABA stimulation of [3H]flunitrazepam binding in the cerebral cortex. None of the treatments affected the cerebellar binding of an imidazobenzodiazepine, [3H]Ro 15-4513. There was an age-dependent decline in the efficacy and potency (EC50) of the GABA enhancement of [3H]flunitrazepam binding in the cerebellum in all treatment groups. Basal binding of [3H]flunitrazepam to hippocampal and cerebellar membranes as well as binding of [3H]Ro 15-4513 to cerebellar membranes was also decreased as a function of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Taira
T
T
University of Helsinki, Department of Physiology, Finland.
Uusi-Oukari
M
M
Korpi
E R
ER
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001386:Azides / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D015430:Weight Gain / Q000187:drug effects
D001386:Azides; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D009118:Muscimol; D000431:Ethanol; D005445:Flunitrazepam; C042957:Ro 15-4513