Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885 improves memory formation in an autoshaping learning task.
In this work we aimed to re-examine the 5-HT6 receptor role, by testing the selective antagonists SB-357134 (1-30 mg/kg p.o.) and SB-399885 (1-30 mg/kg p.o.) during memory consolidation of conditioned responses (CR%), in an autoshaping Pavlovian/instrumental learning task. Bioavailability, half-life and minimum effective dose to induce inappetence for SB-357134 were 65%, 3.4 h, and 30 mg/kg p.o., and for SB-399885 were 52%, 2.2 h, and 50 mg/kg p.o., respectively. Oral acute and chronic administration of either SB-357134 or SB-399885 improved memory consolidation compared to control groups. Acute administration of SB-357134, at 1, 3, 10 and 30 mg/kg, produced a CR% inverted-U curve, eliciting the latter dose a 7-fold increase relative to saline group. Acute injection of SB-399885 produced significant CR% increments, being 1 mg/kg the most effective dose. Repeated administration (7 days) of either SB-357134 (10 mg/kg) or SB-399885 (1 mg/kg) elicited the most significant CR% increments. Moreover, modeling the potential therapeutic benefits of 5-HT6 receptor blockade, acute or repeated administration of SB-399885, at 10 mg/kg reversed memory deficits produced by scopolamine or dizocilpine, and SB-357134 (3 and 10 mg/kg) prevented amnesia and even improved performance. These data support the notion that endogenously 5-HT acting, via 5-HT6 receptor, improves memory consolidation.
Perez-García
Georgina
G
Deparment of Pharmacobiology, CINVESTAV-IPN, Tenorios # 235, Granjas Coapa, México City 14330, México.
Meneses
Alfredo
A
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D010879:Piperazines; D011985:Receptors, Serotonin; D012601:Scopolamine; D012702:Serotonin Antagonists; D013449:Sulfonamides; C422502:N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide; D000096926:Benzenesulfonamides; C503990:SB 399885; C097216:serotonin 6 receptor