5-HT6 receptor blockade differentially affects scopolamine-induced deficits of working memory, recognition memory and aversive learning in mice.
Psychopharmacology. 2012-02-25; 222(1): 99-115
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1. Psychopharmacology (Berl). 2012 Jul;222(1):99-115. doi:
10.1007/s00213-011-2627-3. Epub 2012 Feb 25.
5-HT6 receptor blockade differentially affects scopolamine-induced deficits of
working memory, recognition memory and aversive learning in mice.
Da Silva Costa-Aze V(1), Quiedeville A, Boulouard M, Dauphin F.
(1)Groupe Mémoire et Plasticité Comportementale-GMPc, EA 4259, Université de Caen
Basse Normandie, Caen 14032, France.
RATIONALE: Blockade of 5-HT6 receptors (5-HT6R) is known to improve cognitive
performances in the rodent. This improvement has been hypothesized to be the
result, at least in part, of a modulation of the cholinergic neurotransmission.
OBJECTIVE: We assessed the effects of 5-HT6R blockade on selected types of memory
relevant to functional deficits of ageing and neurodegenerative diseases, in mice
that present a scopolamine-induced cholinergic disruption of memory.
METHOD: Following the selection of an adequate dose of scopolamine to induce
cognitive deficits, we have studied the effects of the selective 5-HT6R
antagonist SB-271046, alone or in combination with scopolamine, on working memory
(spontaneous alternation task in the T-maze), recognition memory (place
recognition) and aversive learning (passive avoidance).
RESULTS: SB-271046 alone failed to affect working memory, recognition memory and
aversive learning performances. In contrast, SB-271046 was able to reverse the
scopolamine-induced deficits in working memory (only at 30 mg kg⁻¹) and those of
acquisition and retrieval of aversive learning (dose-dependent effect);
scopolamine-induced deficits in episodic-like memory (acquisition and retrieval)
were partially counteracted by 5-HT6R blockade.
CONCLUSION: The modulation between 5-HT6R and the cholinergic system appears to
be predominant for working memory and aversive learning, but not for other types
of memory (i.e. episodic-like memory). Interactions between 5-HT6R and
alternative neurotransmission systems (i.e. glutamatergic system) should be
further studied. The respective involvement of these interactions in the memory
disorders related to ageing and neurodegenerative diseases is of pivotal
importance regarding the possible use of 5-HT6R antagonists in the treatment of
memory disorders in humans.
PMID: 22367167 [Indexed for MEDLINE]