on memory and enables spatial learning to rapidly increase neural
cell adhesion molecule (NCAM) expression in the hippocampus of rats
Conboy L, Tanrikut C, Zoladz PR, Campbell AM,
Park CR, Gabriel C, Mocaer E, Sandi C, Diamond DM.
Laboratory of Behavioural Genetics,
Brain Mind Institute, EPFL,
Int J Neuropsychopharmacol. 2008 Aug 18:1-13.
Agomelatine, a novel antidepressant with established clinical efficacy,
acts as a melatonin receptor agonist and 5-HT2C receptor antagonist.
As stress is a significant risk factor in the development of
depression, we sought to determine if chronic agomelatine treatment
would block the stress-induced impairment of memory in rats trained
in the radial-arm water maze (RAWM), a hippocampus-dependent spatial
memory task. Moreover, since neural cell adhesion molecule (NCAM) is
known to be critically involved in memory consolidation and synaptic
plasticity, we evaluated the effects of agomelatine on NCAM, and
polysialylated NCAM (PSA-NCAM) expression in rats given spatial
memory training with or without predator stress. Adult male rats were
pre-treated with agomelatine (10 mg/kg i.p., daily for 22 d),
followed by a single day of RAWM training and memory testing. Rats
were given 12 training trials and then they were placed either in
their home cages (no stress) or near a cat (predator stress). Thirty
minutes later the rats were given a memory test trial followed
immediately by brain extraction. We found that: (1) agomelatine
blocked the predator stress-induced impairment of spatial memory; (2)
agomelatine-treated stressed, as well as non-stressed, rats exhibited
a rapid training-induced increase in the expression of synaptic NCAM
in the ventral hippocampus; and (3) agomelatine treatment blocked the
water-maze training-induced decrease in PSA-NCAM levels in both
stressed and non-stressed animals.
This work provides novel observations which indicate that agomelatine
blocks the adverse effects of stress on hippocampus-dependent memory
and activates molecular mechanisms of memory storage in response to a