Furthermore, SI-induced hyperactivity might be predictive for antipsychotic efficacy, as current treatment was effective in the model. Finally, using LY404039, a compound in development against Pifithrin-�� research buy schizophrenia, we have shown that the hyperactivity assay is sensitive to potential novel mechanisms of action. Thus, SI-induced hyperactivity might be a robust and novel in vivo screening assay of antipsychotic efficacy.”
“Rationale Neuronal plasticity is associated with depression, probably as a result of modified expression of proteins
important for cellular resiliency. It is therefore important to establish if and how antidepressant drugs may be able to regulate these mechanisms in order to achieve relevant clinical effects.
Objective We investigated the effects of chronic treatment with agomelatine (an MT(1)/MT(2) receptor agonist and 5-HT(2C) receptor antagonist) on the brain-derived neurotrophic factor (BDNF), fibroblast growth factor (FGF-2), and activity-regulated cytoskeleton-associated protein (Arc).
Methods Animals were treated for 21 days with agomelatine, venlafaxine, or a vehicle and sacrificed 1 h (6 p.m.) or 16 h after the last injection (9 a.m.) to evaluate the messenger RNA (mRNA) and protein expression of these neuroplastic markers in the hippocampus and prefrontal learn more cortex.
Results Agomelatine, but not venlafaxine, produced major transcriptional changes in the hippocampus, where significant
up-regulations of BDNF and FGF-2 were observed. Both drugs up-regulated the Arc transcription levels. No effects were observed in the prefrontal cortex. Instead, the levels of BDNF protein were elevated by agomelatine in both regions: the effects of the drug on mRNA levels in the hippocampus and cortex are different, while the effects on the protein seem to have the same cumulative result, suggesting different modulatory mechanisms in the two regions.
Conclusions Our data provide new information regarding the molecular mechanisms that contribute to the chronic effects
of the new antidepressant agomelatine on brain function. The ability LY3039478 clinical trial of agomelatine to modulate the expression of these neuroplastic molecules, which follows a circadian rhythm, may contribute to its antidepressant action.”
“Rationale Valproate is widely used in the treatment of epilepsy, bipolar disorder, and chronic pain disorders, but its exact mechanisms of action is still incompletely understood.
Objectives Here we used transcranial magnetic stimulation to explore effects of a single dose of 800 mg valproate on motor cortex excitability in healthy volunteers.
Methods Motor threshold, peripheral maximum M-wave, cortical silent period short intracortical inhibition, intracortical facilitation, and motor evoked potential recruitment were assessed before and 1.5 h after the administration of valproate in 15 (eight male, seven female) healthy volunteers.