Age-dependent effects of serotonin-1A receptor gene deletion in spatial learning abilities in mice

Mathieu Wolff, Pierre Costet, Cornelius Gross, René Hen, Louis Segu, Marie-Christine Buhot
Molecular Brain Research. 2004-11-01; 130(1-2): 39-48
DOI: 10.1016/j.molbrainres.2004.07.012

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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.

Author information:
(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.

DOI: 10.1016/j.molbrainres.2004.07.012
PMID: 15519675 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus