Effects of pentobarbital on the expression of GABAA receptor beta 1 mRNA in the hippocampus: differential responses of CA1 and CA3.

Abstract

Effects of barbiturates have been linked to the inhibitory GABAA receptor in the brain. The present study examines changes in the expression of GABAA receptor in the hippocampus of pentobarbital treated rat. Intraperitoneal pentobarbital injections were administered once daily for 9 days at an increasing dose schedule, 30 mg/kg at day 1-3, 60 mg/kg day 4-6, and 90 mg/kg day 7-9. Within each of the three dosage periods, the duration of sleep and extent of reduction in body temperature of the rats decreased with time. Two hours after the 9th injection, 3H-muscimol binding of the hippocampal homogenates of the animals showed that the maximal number of binding sites (Bmax), 10.2 +/- 1.6 pmol/mg protein, was not significantly greater than 9.5 +/- 1.2 of saline control, but strikingly about 7-fold control level of beta 1 mRNA was seen in the pyramidal cells of CA1 and CA2, as revealed by in situ hybridization analysis with digoxigenin-cRNA probes. However, when the rats were withdrawn from pentobarbital injection for 24 hours and 7 days, the Bmax of the hippocampi was lowered to 7.3 +/- 1.0 and 5.1 +/- 0.7, respectively, and the expression of beta 1 mRNA in CA1-2 returned toward control. The pentobarbital treatment did not significantly alter the affinity of the radioligand to the receptor in the hippocampus and the expression of beta 1 mRNA in CA3 and CA4. The results suggest the plasticity of the beta 1 mRNA in CA1-2 as well as differential involvement of CA1-2 and CA3-4 in response to the pentobarbital perturbation.