Delay-dependent working memory impairment in young-adult and aged 5-HT1BKO mice as assessed in a radial-arm water maze
1. Learn Mem. 2003 Sep-Oct;10(5):401-9.
Delay-dependent working memory impairment in young-adult and aged 5-HT1BKO mice
as assessed in a radial-arm water maze.
Wolff M(1), Benhassine N, Costet P, Hen R, Segu L, Buhot MC.
(1)Centre National de la Recherche Scientifique-UMR 5106, Laboratoire de
Neurosciences Cognitives, Universitéde Bordeaux 1, 33405 Talence cedex, France.
Serotonin (5-HT) plays a modulatory role in mnemonic functions, especially by
interacting with the cholinergic system. The 5-HT1B receptor is a key target of
this interaction. The 5-HT1B receptor knockout mice were found previously to
exhibit a facilitation in hippocampal-dependent spatial reference memory
learning. In the present study, we submitted mice to a delayed spatial working
memory task, allowing the introduction of various delays between an exposure
trial and a test trial. The 5-HT1BKO and wild-type mice learned the task in a
radial-arm water maze (returning to the most recent presented arm containing the
escape platform), and exhibited a high level of performance at delays of 0 and 5
min. However, at the delay of 60 min, only 5-HT1BKO mice exhibited an impairment.
At a delay of 90 min, all mice were impaired. Treatment by scopolamine (0.8
mg/kg) 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. The
22-month-old wild-type and knockout mice exhibited an impairment at short delays
(5 and 15 min). The effect of the mutation affected both young-adult and aged
mice at delays of 15, 30, and 60 min. Neurobiological data show that stimulation
of the 5-HT1B receptor inhibits the release of acetylcholine in the hippocampus,
but stimulates this in the frontal cortex. This dual function might, at least in
part, explain the opposite effect of the mutation on reference memory
(facilitation) and delay-dependent working memory (impairment). These results
support the idea that cholinergic-serotonergic interactions play an important
role in memory processes.
PMID: 14557613 [Indexed for MEDLINE]