Hippocampus is a major site of combined anticonvulsant-antidepressant action of selective ionotropic and metabotrobic glutamate receptor ligands.

Introduction
Glutamate regulates the brain's excitability via both ionotropic (iGluR, i.e. NMDA, AMPA and kainate) and metabotropic (mGluR) receptors and is also a key player in epilepsy processes (1, 2). Refractory epilepsy has a major impact on daily, social and psychosocial life of the patients. Co-morbid depression significantly correlates with a poor quality of life among epileptic patients (3) and suicide seems one of their leading causes of death (4). Key roles for monoamines in depression have been established for decades since monoamine oxidase inhibitors and re-uptake blockers proved their clinical efficacy.
Nowadays neurobiological relationships between epilepsy and affective disorders receive increased attention. After all, these disorders often develop in the same limbic or cortical brain regions. Facilitation of central serotonin (5-HT) and noradrenalin is associated with both anticonvulsant and antidepressant effects (5). Several lines of evidence also support a role for dopamine (DA) in depression and epilepsy (6). In this context, we recently investigated the effects of exogenous intrahippocampally administered monoamines on seizure control (7). We defined a narrow concentration range of extracellular DA and 5-HT in which all rats were protected from pilocarpine-induced seizures. Subsequently, we examined whether increases in endogenous hippocampal monoamines exerted similar actions. We showed that the selective DA re-uptake blocker GBR-12909 and the selective 5-HT re-uptake blocker citalopram clearly possessed anticonvulsant properties against limbic seizures (8). Interestingly, anticonvulsant threshold concentrations of both GBR-12909 and citalopram were accompanied by significant increases in extracellular DA or 5-HT levels in the hippocampus of the conscious rats.
These findings prompted us to investigate whether selective iGluR and mGluR ligands with proven anticonvulsant properties exerted antidepressant-like activities within the forced swim test and whether these ligands were able to facilitate DA and 5-HT release in the rat hippocampus as sampled with microdialysis.