Direct enhancement of hippocampal dopamine or serotonin levels as a pharmacodynamic measure of combined antidepressant–anticonvulsant action

Relevance of the metabotropic glutamate receptor (mGluR5) in the regulation of NREM-REM sleep cycle and homeostasis: Evidence from mGluR5 (−/−) mice

“…In addition, direct blockade of the NMDA receptor with MK-801 or ketamine elicited massive slow wave sleep and homeostatic recovery evoked by high metabolic activity [26,27]. Moreover, the allosteric antagonist of mGluR5 MTEP ([(2-methyl-1, 3-thiazol-4-yl)ethynyl]pyridine) has been shown to evoke 5-HT release in the hippocampus and frontal cortex [28,29], which may contribute to sleep facilitating effects following the activation of 5HT2A/2C receptors. Thus, the enhanced sleep and the deficiency in REM sleep observed in the mGluR5 (−/−) mice may derive from a chronic imbalance in the interaction of mGluR5 with components of the brain's ascending and descending systems, of which activities are known to trigger or to dampen the occurrence of NREM and REM sleep states.…”

The catechol-O-methyltransferase Val(108/158)Met polymorphism affects antidepressant response to paroxetine in a naturalistic setting

“…Given that the noradrenergic, dopaminergic and serotoninergic systems have reciprocal interactions, it is virtually impossible to act on a specific neuronal element without affecting in a cascade effect the two other systems (Tremblay and Blier 2006). In rodents, serotonergic antidepressants increased dopamine (DA) levels in the hippocampus (Smolders et al 2008) and norepinephrine (NE) levels in the frontal cortex (Kobayashi et al 2008), and in an animal model of depression (Flinders sensitive rats), serotonin (5-HT) and serotonergic drugs facilitated DA release in the nucleus accumbens (Zangen et al 2001), with the 5-HT-induced DA release, but not basal DA levels, being proportional to the improvement of depressive-like behaviours (Dremencov et al 2004). These data suggested that an enhancement in catecholaminergic neurotransmission, stimulated by serotonergic drugs, could contribute to the overall antidepressant effect.…”

Effect of acute and chronic treatment with milnacipran potentiates the anticonvulsant activity of conventional antiepileptic drugs in the maximal electroshock-induced seizures in mice

“…In fact, increased hippocampal dopamine was reported to attenuate limbic seizures via D 2 receptor stimulation (Clinckers et al 2004). Moreover, increases in hippocampal dopamine and serotonin may serve as pharmacodynamic markers of combined anticon- Smolders et al 2008). Interestingly, also lamotrigine and carbamazepine, recognized mood stabilizers, increase hippocampal dopamine concentration .…”