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 GABA_A agonist, and with ethanol, also shown to have a GABAergic profile of action, on subsequent behavior and on the binding parameters of GABA_A 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. The results suggest that muscimol exposure induces a transient change in GABA_A receptor sensitivity. Also, open-field behavior, ethanol consumption and GABA_A receptor mechanisms may be interrelated in the rat.