Long-term treatment with antidepressants, but not environmental stimulation, induces expression of NP2 mRNA in hippocampus and medial habenula.

In experimental settings, antidepressant treatment as well as a stimulating environment has a positive influence on cognition and hippocampal plasticity. One putative mediator of this process is Neuronal Pentraxin 2 (NP2, Narp), known to mediate clustering of glutamatergic AMPA receptors at synapses, and demonstrated to play a role in activity-dependent synaptogenesis and synaptic plasticity. This study demonstrates that NP2 mRNA is robustly expressed in all hippocampal subregions and the medial habenula (MHb), both regions implicated in cognitive functions. Furthermore, NP2 mRNA expression is upregulated in the hippocampal subregions as well as in the MHb after long-term treatment with different antidepressant drugs regardless of monoaminergic profile, suggesting NP2 as a common mode of action of different antidepressant drugs. This effect occurs at the time frame where clinical response is normally achieved. In contrast, neither environmental enrichment nor deprivation has any influence on long-term NP2 mRNA expression. These findings support an involvement of NP2 in the pathway of antidepressant-induced plasticity, but not EE-induced plasticity; that NP2 might constitute a common link for the action of different types of antidepressant drugs and that the MHb could be a putative region for further studies of NP2.