Age-dependent effects of serotonin-1A receptor gene deletion in spatial learning abilities in mice
Molecular Brain Research. 2004-11-01; 130(1-2): 39-48
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1. Brain Res Mol Brain Res. 2004 Nov 4;130(1-2):39-48.
Age-dependent effects of serotonin-1A receptor gene deletion in spatial learning
abilities in mice.
Wolff M(1), Costet P, Gross C, Hen R, Segu L, Buhot MC.
(1)Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux
1, Avenue des Facultés, 33405 Talence cedex, France.
The serotonin (5-hydroxytryptamine, 5-HT) receptor 1A is involved in many
physiological functions, including the regulation of learning and memory by
acting either as an autoreceptor located on 5-HT neurons (raphe nuclei) or as a
heteroreceptor on non-5-HT neurons, mainly in the hippocampal formation. To
investigate whether the effects of 5-HT via 5-HT1A receptors on learning are
age-sensitive, we evaluated the performance of young-adult (3 months old) and
aged (22 months old) 5-HT1A knockout (KO) mice and their homologous wild types
(WT) in the hippocampal-dependent spatial reference memory version of the Morris
water maze. We demonstrated that young-adult 5-HT1AKO mice exhibit an impairment
in learning and retention of the spatial task, as compared to WT mice, without
showing any sign of change in their sensori-motor and locomotor abilities or
motivation. This genotype effect does not persist during aging. In fact, aged
5-HT1AKO mice seem to be slightly facilitated during the early stages of
learning. These results are consistent with a possible prevalence of 5-HT1A raphe
functions in learning and memory abilities of young-adult animals, since the
effects of the mutation on mice performance (impairment) are opposite to those
found after intra-raphe injection of 5-HT1A agonists (facilitation), and with
data showing increased activity of 5-HT neurons in 5-HT1AKO mice. The reduced
effect of the mutation in aged animals possibly reflects the lower efficacy of
autoreceptors due to aging and/or a prevalence of hippocampal heteroreceptors.
PMID: 15519675 [Indexed for MEDLINE]