, Volume 170, Issue 4, pp 358-367

Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790

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Abstract

Rationale

Accumulating evidence suggests a potential role for the 5-HT6 receptor in cognitive function and the potential use of 5-HT6 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-HT6 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 D2 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 (T1) and a novel and familiar object during trial 2 (T2). The time spent exploring the two objects in each trial was measured and novel object discrimination assessed in T2.

Results

In the absence of drug all rats spent an equal time exploring the two identical objects in T1 but more time exploring the novel object in T2. Scopolamine (but not N-methylscopolamine) and raclopride both produced a dose-dependent reduction in novel object discrimination whilst the 5-HT6 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-HT6 receptor in the regulation of cognitive function.