| Title | The pharmacological properties of the GABAA / benzodiazepine receptor complex differ between dorsal and ventral rat hippocampus | |
| Authors | Konstantinos Sarantis¹, Evangelos Sotiriou¹, Constantinos Papatheodoropoulos¹, Nikolaos Matsokis² and Fevronia Angelatou¹
1. Department of Physiology, School of Medicine and 2. Lab. of Human and Animal Physiology, Department of Biology, University of Patras, Greece |
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| Citation | Sarantis, Κ., Sotiriou, Ε., Papatheodoropoulos, C., Matsokis, N., Angelatou, F.: The pharmacological properties of the GABAA / benzodiazepine receptor complex differ between dorsal and ventral rat hippocampus, Epitheorese Klin. Farmakol. Farmakokinet. 20(2): 311-313 (2006) | |
| Publication Date | Accepted for publication: 19-20 May 2006 | |
| Full Text Language | English | |
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| Keywords | Septotemporal, hippocampus, benzodiazepines, GABAA subtypes, pharmacology. | |
| Other Terms | review article | |
| Summary | Several studies have indicated a functional differentiation between dorsal (DH) and ventral (VH) rat hippocampus. Pharmacological studies have shown that the α1-GABAA receptor subtype is associated with the anticonvulsant and sedative effects of benzodiazepines (BZs), whereas the α2-subtype is associated with the anxiolytic effects of BZs. A recent study indicates that the α1/β2 GABAA receptor subtype dominates in the DH, while the α2/β1 subtype prevails in the VH (1). We therefore studied the possible differences in the pharmacological properties and receptor binding parameters of the GABAA receptor subtypes between DH and VH, by examining: a) the specific binding of [3H]-flunitrazepam (BZ sites agonist), by using quantitative autoradiography, b) the kinetic parameters of [3H]-flunitrazepam specific binding, by using the wipe off technique and c) the competitive displacement of [3H]-flunitrazepam binding by using zolpidem (a specific agonist of α1-subtype) and the enhancement of [3H]-flunitrazepam binding by using etomidate (a selective positive modulator of β2 subunit), in an autoradiographical saturation kinetic study. Our results showed in VH compared to the DH: a) lower level of [3H]-flunitrazepam binding in CA1, CA3 and DG regions, as obtained from our autoradiographic results, b) higher KD value for [3H]-flunitrazepam specific binding in CA1 region and no differences in the Bmax value, c) higher IC50 value for zolpidem and d) higher EC50 value for etomidate. In conclusion, the lower affinity of GABAA receptors for [3H]-flunitrazepam binding, as well as the lower affinity for zolpidem and etomidate binding observed in VH compared to DH, support the evidence that the α1/β2 GABAA receptor subtype dominates in DH and the α2/β1 subtype prevails in VH and suggest differential pharmacological effects of the benzodiazepines in DH compared to VH. | |
| References | 1. Sotiriou E., Papatheodoropoulos C., Angelatou F.: J. Neurosci. Res. 82 : 690-700 (2005)
2. Moser M.B., Moser E.I.: Hippocampus 8: 608-619 (1998) 3. Papatheodoropoulos C., Kostopoulos G.: Neurosci. Lett. 8, 319(1) : 17-20 (2002) 4. Sieghart W.: Pharmacol. Rev. 47: 181-234 (1995) 5. Mohler H., Fritschy J.M., Rudolph U.: J. Pharmacol. Exp. Ther. 300: 2-8 (2002) 6. Titulaer M.N., Kamphuis W., Lopes da Silva F.H.: Neuroscience 68: 399-405 (1995) |
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Online ISSN 1011-6575
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Articles published in this Journal are Indexed or Abstracted in: • Chemical Abstracts • Elsevier’s Bibliographic Databases: Scopus, EMBASE, EMBiology, Elsevier BIOBASE SCImago Journal and Country Rank Factor
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