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

Abstract

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: Marie L Woolley, Charles A Marsden, Andrew J Sleight, Kevin C F Fone
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 170 Issue 4 Pg. 358-67 (Dec 2003) ISSN: 0033-3158 [Print] Germany
• PMID: 13680084 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Antagonists
• Muscarinic Antagonists
• Pyrimidines
• Ro 4-6790
• Serotonin Antagonists
• Raclopride
• Scopolamine

Topics

• Animals
• Behavior, Animal (drug effects)
• Dopamine Antagonists (pharmacology)
• Dose-Response Relationship, Drug
• Drug Interactions
• Male
• Memory (drug effects)
• Muscarinic Antagonists (pharmacology)
• Pyrimidines (pharmacology)
• Raclopride (antagonists & inhibitors)
• Rats
• Scopolamine (antagonists & inhibitors)
• Serotonin Antagonists (pharmacology)