title: The anti-amnesic effects of sigma1 (sigma1) receptor agonists confirmed by in vivo antisense strategy in the mouse.
abstract: The sigma1 (sigma1) receptor cDNA was recently cloned in several animal species, including the mouse. In order to firmly establish the implication of sigma1 receptors in memory, a phosphorothioate-modified antisense oligodeoxynucleotide (aODN) targeting the sigma1 receptor mRNA and a mismatched analog (mODN) were administered intracerebroventricularly for 3 days in mice. Scatchard analyses of in vitro (+)-[3H]SKF-10,047 binding to sigma1 sites showed that Bmax values were significantly decreased in the hippocampus (-58.5%) and cortex (-38.1%), but not in the cerebellum, of aODN treated mice, as compared to saline- or mODN-treated animals. In vivo binding levels were also significantly decreased after aODN treatment in the hippocampus and cortex but not in the cerebellum. The anti-amnesic effects of the selective sigma1 agonists PRE-084 or SA4503 were evaluated against the learning impairments induced by dizocilpine or scopolamine, respectively, using spontaneous alternation behavior and passive avoidance task. The anti-amnesic effects of PRE-084 or SA4503, observed after saline- or mODN-treatment, were blocked after aODN administration. These observations bring a molecular basis to the modulatory role of sigma1 receptors in memory processes.
authors: INSERM U. 336, Behavioral Neuropharmacology group, Institut de Biologie, 4, boulevard Henri IV, 34060, Montpellier, France. maurice@medecine.univ-montp1.fr
authors: T
authors: T
authors: Maurice
authors: V L
authors: VL
authors: Phan
authors: A
authors: A
authors: Privat
mesh_terms: D000647:Amnesia / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001921:Brain / Q000378:metabolism; D016291:Dizocilpine Maleate; D018690:Excitatory Amino Acid Agonists; D066298:In Vitro Techniques; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D009025:Morpholines / Q000627:therapeutic use; D018697:Nootropic Agents / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists*
chemical_list: D018690:Excitatory Amino Acid Agonists; D009025:Morpholines; D018697:Nootropic Agents; D016376:Oligonucleotides, Antisense; D010879:Piperazines; D017480:Receptors, sigma; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; D016291:Dizocilpine Maleate; C012134:SK&F 10047; C101789:SA 4503; D010620:Phenazocine