Spatial learning in the 5-HT1B receptor knockout mouse: Selective facilitation/impairment depending on the cognitive demand
1. Learn Mem. 2003 Nov-Dec;10(6):466-77.
Spatial learning in the 5-HT1B receptor knockout mouse: selective
facilitation/impairment depending on the cognitive demand.
Buhot MC(1), Wolff M, Benhassine N, Costet P, Hen R, Segu L.
Author information:
(1)Centre National de la Recherche Scientifique-Unité Mixte de Recherche 5106,
Laboratoire de Neurosciences Cognitives, Université de Bordeaux 1, 33405 Talence,
France.
Age-related memory decline is associated with a combined dysfunction of the
cholinergic and serotonergic systems in the hippocampus and frontal cortex, in
particular. The 5-HT1B receptor occupies strategic cellular and subcellular
locations in these structures, where it plays a role in the modulation of ACh
release. In an attempt to characterize the contribution of this receptor to
memory functions, 5-HT1B receptor knockout (KO) mice were submitted to various
behavioral paradigms carried out in the same experimental context (water maze),
which were aimed at exposing mice to various levels of memory demand. 5-HT1BKO
mice exhibited a facilitation in the acquisition of a hippocampal-dependent
spatial reference memory task in the Morris water maze. This facilitation was
selective of task difficulty, showing thus that the genetic inactivation of the
5-HT1B receptor is associated with facilitation when the complexity of the task
is increased, and reveals a protective effect on age-related
hippocampal-dependent memory decline. Young-adult and aged KO and wild-type (WT)
mice were equally able to learn a delayed spatial matching-to-sample working
memory task in a radial-arm water maze with short (0 or 5 min) delays. However,
5-HT1BKO mice, only, exhibited a selective memory impairment at intermediate and
long (15, 30, and 60 min) delays. Treatment by scopolamine induced the same
pattern of performance in wild type as did the mutation for short (5 min, no
impairment) and long (60 min, impairment) delays. Taken together, these studies
revealed a beneficial effect of the mutation on the acquisition of a spatial
reference memory task, but a deleterious effect on a working memory task for long
delays. This 5-HT1BKO mouse story highlights the problem of the potential
existence of “global memory enhancers.”
DOI: 10.1101/lm.60203
PMID: 14657258 [Indexed for MEDLINE]