Ž . European Journal of Pharmacology 354 1998 91–97 Pharmacological properties of the GABA receptor complex from brain A ž / ž / regions of hypoemotional Roman high- and hyperemotional low-avoidance rats Rachid Bentareha a , Francisco Araujo a , Diego Ruano a , Peter Driscoll b , Rosa M. Escorihuela c , Adolf Tobena c , Alberto Fernandez-Teruel c , Javier Vitorica a, ) ˜ ´ a Departamento Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, UniÕersidad de SeÕilla, SeÕilla 41012, Spain b Animal Science Institute, ETH-Z, Turnerstrasse 1, Zurich CH-8092, Switzerland ¨ c Medical Psychology Unit, Department of Psychiatry, Toxicology and Forensic Medicine, School of Medicine, Autonomous UniÕersity of Barcelona, 08193 Bellaterra, Barcelona, Spain Received 16 April 1998; revised 29 May 1998; accepted 3 June 1998 Abstract Ž . The pharmacological properties of benzodiazepine binding sites of the g-aminobutyric acid GABA receptor complex from cortical, A Ž . Ž . hippocampal and cerebellar membranes of Roman high-avoidance RHArVerh and Roman low-avoidance RLHrVerh rats were w 3 x Ž investigated. No major differences between the two lines were found in the binding parameters of H flunitrazepam a non-selective . w 3 x Ž . w 3 x w xw x agonist , H zolpidem a Type I selective agonist or H ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazol 1,5-a - 1,4 benzodi- Ž .Ž . azepine-3-carboxylate Ro15-4513 a partial inverse agonist . Neither the K values nor the B for these ligands differed between d max RHArVerh and RLArVerh rats in any of the brain regions studied. As a result, the proportion of Type I binding sites in cortical and hippocampal membranes of RHArVerh and RLArVerh rats or the ‘diazepam-sensitive’ and the ‘diazepam-insensitive’ binding sites in w 3 x w 3 x w 3 x Ž cerebellar membranes, calculated from the H flunitrazepam and H zolpidem maximal binding sites or from H Ro15-4513 binding in . the absence or in presence of diazepam , respectively, was also similar. Furthermore, there were no differences between the two rat lines Ž w 3 x . in the allosteric interactions between GABA and the benzodiazepine binding sites labeled with H flunitrazepam in all three areas tested Ž w 3 x . or the Type I binding sites labeled with H zolpidem in the hippocampus. In contrast, RLArVerh rats showed a significant reduction in w 3 x the allosteric interactions between GABA and H zolpidem binding sites in the cortex. As a whole, these results indicate the absence of generalized between-line differences in the GABA receptor complex showing, at the same time, the existence of some specific A differences in allosterism within the GABA complex. These differences may contribute to the divergent emotional responses which A characterize the RHArVerh and RLArVerh rat lines. q 1998 Elsevier Science B.V. All rights reserved. w 3 x w 3 x w 3 x Keywords: GABA receptor complex; H Flunitrazepam; H Zolpidem; Diazepam; H Ro15-4513; Cortex; Hippocampus; Cerebellum; Emotionality; A Ž .Ž . RHArVerh rats ; RLArVerh rats 1. Introduction The Wistar-derived Roman high- and low-avoidance Ž . RHArVerh and RLArVerh, respectively rat lines have been selected and bred in Switzerland since 1972 for rapid Ž . acquisition RHArVerh vs. extremely poor acquisition Ž . Ž . RLArVerh of two-way active shuttle box avoidance Ž . Driscoll and Battig, 1982 , using stock previously devel- ¨ ) Corresponding author. Tel.: q34-95-4556770; Fax: q34-95-4233765 Ž oped by Bignami and Broadhurst Bignami, 1965; Broad- . hurst and Bignami, 1965 . In accordance with the evidence showing that early, two-way active avoidance acquisition is mediated by fear- Ž . motivated responses Fernandez-Teruel et al., 1991a , ex- ´ tensive research conducted with the RomanrVerh rats has led to the conclusion that the RLArVerh line is more emotionally reactive than the RHArVerh line. For exam- ple, RLArVerh rats show, as compared to RHArVerh animals, a more pronounced tachycardia when exposed to various unconditioned stressful conditions, a more intense 0014-2999r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved.