TY - JOUR T1 - Acute Pentylenetetrazol Injection Reduces Rat GABA<sub>A</sub>Receptor mRNA Levels and GABA Stimulation of Benzodiazepine Binding with No Effect on Benzodiazepine Binding Site Density JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1626 LP - 1633 VL - 289 IS - 3 AU - Laura A. Walsh AU - Ming Li AU - Tai-Jun Zhao AU - Ted H. Chiu AU - Howard C. Rosenberg Y1 - 1999/06/01 UR - http://jpet.aspetjournals.org/content/289/3/1626.abstract N2 - The effects of a single convulsive dose of pentylenetetrazol (PTZ, 45 mg/kg i.p.) on rat brain γ-aminobutyric acid type A (GABAA) receptors were studied. Selected GABAAreceptor subunit mRNAs were measured by Northern blot analysis (with β-actin mRNA as a standard). Four hours after PTZ, the GABAA receptor γ2-mRNA was decreased in hippocampus, cerebral cortex, and cerebellum; α1-mRNA was decreased in cerebellum; and β2 subunit mRNA was decreased in cortex and cerebellum. The α5 subunit mRNA level was not altered. Those mRNAs that had been reduced were increased in some brain regions at the 24-h time point, and these changes reverted to control levels by 48 h. PTZ effect on GABAA receptors was also studied by autoradiographic binding assay with the benzodiazepine agonist [3H]flunitrazepam (FNP), the GABAA agonist [3H]muscimol, and the benzodiazepine antagonist [3H]flumazenil. There was an overall decrease in [3H]FNP binding 12 but not 24 h after PTZ treatment. In contrast, [3H]muscimol binding was minimally affected, and [3H]flumazenil binding was unchanged after PTZ treatment. Additional binding studies were performed with well-washed cerebral cortical homogenates to minimize the amount of endogenous GABA. There was no PTZ effect on specific [3H]FNP binding. However, there was a significant reduction in the stimulation of [3H]FNP binding by GABA. The results showed that an acute injection of PTZ caused transient changes in GABAAreceptor mRNA levels without altering receptor number but affected the coupling mechanism between the GABA and benzodiazepine sites of the GABAA receptor. The American Society for Pharmacology and Experimental Therapeutics ER -