The neuroprotective effects of riluzole, a novel antiglutamate, has been demonstrated in a model of ischemia induced in female Mongolian gerbils by transient bilateral carotid occlusion. Riluzole was administered at a dose of 4 mg/kg, i.p., just before, 4 hr after, and for the 14 d following the transient bilateral carotid occlusion (10 min). The functional sequelae of ischemic damage were assessed using a memory test (passive avoidance) and the extent of neuronal damage by histological examination and quantitative autoradiography of muscarinic cholinergic receptors in the hippocampus. The performance of the ischemic gerbils in the memory test was about half that of control animals. This memory deficit was completely reversed in animals treated with riluzole. This protective effect of riluzole was confirmed by histological and autoradiographic studies. The neuronal degeneration of CA1 pyramidal cells in the hippocampus observed in the ischemic group was not seen in the riluzole-treated animals, which resembled the control group. This neuronal degeneration in the CA1 area was confirmed by a quantitative measurement of muscarinic receptors: The binding was decreased by a third in the lacunosum moleculare, the stratum oriens, and the stratum radiatum. By contrast in riluzole-treated gerbils, this decrease was reversed by 50%. Finally, a clear-cut correlation was found between the deficit in the memory test and the decrease in muscarinic receptor binding in the CA1 fields. These results are compatible with the idea that glutamic acid may be involved in the neuronal degeneration of the hippocampus following ischemia, and could be foreseeable.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

No abstract

Suriclone is a potent non-benzodiazepine anxiolytic belonging to the cyclopyrrolone family. This study examines the distribution and properties of [ Unlike benzodiazepine (BZ) agonists, [3H1-suriclone binding to rat brain sections was not increased in the presence of GABA, and unlike imidazopyridines such as alpidem, suriclone was unable to discriminate between the BZ, and BZ, phenotype of the GABA, receptor. The autoradiographic distribution of [3H]-suriclone binding sites in the rat brain was heterogeneous and relatively similar to that previously described for GABA, receptors labelled by benzodiazepines; some regions, however, such as certain cortical areas, displayed a different labelling.The highest densities were found in frontal, occipital, parietal, and cingulate cortices (layers I, II, Ill, IV), in the molecular layer of the cerebellum, in the superior colliculus and in the hippocampus. Moderate binding densities appeared in numerous areas such as the inferior colliculus, the central grey, the dorsal raphe, and the hypothalamus whereas caudate putamen, globus pallidus, and thalamic nuclei displayed a low density of [3H]-suriclone binding sites.(0 1995 Wiley-Liss, Inc.