RATIONALE: Accumulating evidence suggests a potential role for the 5-HT(6 )receptor in cognitive function and the potential use of 5-HT(6) receptor antagonists in the treatment of learning and memory disorders. OBJECTIVES: The aim of the current study was to investigate the effect of the selective 5-HT(6) receptor antagonist, Ro 04-6790, on both the performance of normal adult rats and restoration of a pharmacological disruption of memory function produced by the non-selective muscarinic receptor antagonist, scopolamine, or the dopamine D(2) receptor antagonist, raclopride, in a rodent model of recognition memory. METHODS: Passive, perceptually based, recognition memory was assessed using a novel object discrimination task. Following habituation to an arena, rats were presented with two identical objects during trial 1 (T(1)) and a novel and familiar object during trial 2 (T(2)). The time spent exploring the two objects in each trial was measured and novel object discrimination assessed in T(2). RESULTS: In the absence of drug all rats spent an equal time exploring the two identical objects in T(1) but more time exploring the novel object in T(2). Scopolamine (but not N-methylscopolamine) and raclopride both produced a dose-dependent reduction in novel object discrimination whilst the 5-HT(6) receptor antagonist, Ro 04-6790, had no effect on discrimination when given alone but completely reversed the scopolamine- but not the raclopride-induced deficit. CONCLUSION: This study demonstrates that acute administration of Ro 04-6790 reverses a cholinergic but not a dopaminergic deficit in a rodent model of recognition memory and provides further support for a role of the 5-HT(6) receptor in the regulation of cognitive function.
RATIONALE: Accumulating evidence suggests a potential role for the 5-HT(6 )receptor in cognitive function and the potential use of 5-HT(6) receptor antagonists in the treatment of learning and memory disorders. OBJECTIVES: The aim of the current study was to investigate the effect of the selective 5-HT(6) receptor antagonist, Ro 04-6790, on both the performance of normal adult rats and restoration of a pharmacological disruption of memory function produced by the non-selective muscarinic receptor antagonist, scopolamine, or the dopamine D(2) receptor antagonist, raclopride, in a rodent model of recognition memory. METHODS: Passive, perceptually based, recognition memory was assessed using a novel object discrimination task. Following habituation to an arena, rats were presented with two identical objects during trial 1 (T(1)) and a novel and familiar object during trial 2 (T(2)). The time spent exploring the two objects in each trial was measured and novel object discrimination assessed in T(2). RESULTS: In the absence of drug all rats spent an equal time exploring the two identical objects in T(1) but more time exploring the novel object in T(2). Scopolamine (but not N-methylscopolamine) and raclopride both produced a dose-dependent reduction in novel object discrimination whilst the 5-HT(6) receptor antagonist, Ro 04-6790, had no effect on discrimination when given alone but completely reversed the scopolamine- but not the raclopride-induced deficit. CONCLUSION: This study demonstrates that acute administration of Ro 04-6790 reverses a cholinergic but not a dopaminergic deficit in a rodent model of recognition memory and provides further support for a role of the 5-HT(6) receptor in the regulation of cognitive function.
Authors: M G Russell; R J Baker; L Barden; M S Beer; L Bristow; H B Broughton; M Knowles; G McAllister; S Patel; J L Castro Journal: J Med Chem Date: 2001-11-08 Impact factor: 7.446
Authors: R Kohen; M A Metcalf; N Khan; T Druck; K Huebner; J E Lachowicz; H Y Meltzer; D R Sibley; B L Roth; M W Hamblin Journal: J Neurochem Date: 1996-01 Impact factor: 5.372
Authors: M Ruat; E Traiffort; J M Arrang; J Tardivel-Lacombe; J Diaz; R Leurs; J C Schwartz Journal: Biochem Biophys Res Commun Date: 1993-05-28 Impact factor: 3.575
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Authors: David J G Watson; Florence Loiseau; Manuela Ingallinesi; Mark J Millan; Charles A Marsden; Kevin C F Fone Journal: Neuropsychopharmacology Date: 2011-10-26 Impact factor: 7.853