Effects of pentobarbital on the expression of GABAA receptor β1 mRNA in the hippocampus: Differential responses of CA1 and CA3

✍ Scribed by Hsiang-Shu Yin; Yu-Ping Lee

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 470 KB
• Volume: 29
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199808)29:4<371::aid-syn9>3.0.co;2-2

✦ Synopsis

Effects of barbiturates have been linked to the inhibitory GABA A receptor in the brain. The present study examines changes in the expression of GABA A 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, 3 H-muscimol binding of the hippocampal homogenates of the animals showed that the maximal number of binding sites (B max ), 10.2 Ϯ 1.6 pmol/mg protein, was not significantly greater than 9.5 Ϯ 1.2 of saline control, but strikingly about 7-fold control level of ␤ 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 However, when the rats were withdrawn from pentobarbital injection for 24 hours and 7 days, the B max of the hippocampi was lowered to 7.3 Ϯ 1.0 and 5.1 Ϯ 0.7, respectively, and the expression of ␤ 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 ␤ 1 mRNA in CA3 and CA4. The results suggest the plasticity of the ␤ 1 mRNA in CA1-2 as well as differential involvement of CA1-2 and CA3-4 in response to the pentobarbital perturbation.