Antiallodynic effect induced by [6]-gingerol in neuropathic rats is mediated by activation of the serotoninergic system and the nitric oxide-cyclic guanosine monophosphate-adenosine triphosphate-sensitive K+ channel pathway.

The present study evaluated the possible antiallodynic effect induced by [6]-gingerol in rats with L5-L6 spinal nerve ligation (SNL). Moreover, we determined the possible mechanism underlying the antiallodynic effect induced by [6]-gingerol in neuropathic rats. The animals underwent L5-L6 SNL for the purpose of developing tactile allodynia. Tactile allodynia was measured with von Frey filaments. Intrathecal administration of [6]-gingerol reversed SNL-induced tactile allodynia. The [6]-gingerol-induced antiallodynic effect was prevented by the intrathecal administration of methiothepin (30 µg per rat; nonselective 5-hydroxytryptamine [5-HT] antagonist), WAY-100635 (6 µg per rat; selective 5-HT1A receptor antagonist), SB-224289 (5 µg per rat; selective 5-HT1B receptor antagonist), BRL-15572 (4 µg per rat; selective 5-HT1D receptor antagonist), and SB-659551 (6 µg per rat; selective 5-HT5A receptor antagonist), but naloxone (50 µg per rat; nonselective opioid receptor antagonist) did not prevent the [6]-gingerol-induced antiallodynic effect. Moreover, intrathecal administration of Nω-nitro-l-arginine methyl ester (100 µg per rat; nonselective nitric oxide [NO] synthase inhibitor), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 µg per rat; inhibitor of guanylate cyclase), and glibenclamide (50 µg per rat; channel blocker of adenosine triphosphate [ATP]-sensitive K+ channels) prevented the [6]-gingerol-induced antiallodynic effect. These data suggest that the antiallodynic effect induced by [6]-gingerol is mediated by the serotoninergic system involving the activation of 5-HT1A/1B/1D/5A receptors, as well as the NO-cyclic guanosine monophosphate-ATP-sensitive K+ channel pathway but not by the opioidergic system.

Modulation of the consolidation and reconsolidation of fear memory by three different serotonin receptors in hippocampus.

The process of memory formation is complex and highly dynamic. During learning, the newly acquired information is found in a fragile and labile state. Through a process known as consolidation, which requires specific mechanisms such as protein synthesis, the memory trace is stored and stabilized. It is known that when a consolidated memory is recalled, it again becomes labile and sensitive to disruption. To be maintained, this memory must undergo an additional process of restabilization called reconsolidation, which requires another phase of protein synthesis. Memory consolidation has been studied for more than a century, while the molecular mechanisms underlying the memory reconsolidation are starting to be elucidated. For this, is essential compare the participation of important neurotransmitters and its receptors in both processes in brain regions that play a central role in the fear response learning. With focus on serotonin (5-HT), a well characterized neurotransmitter that has been strongly implicated in learning and memory, we investigated, in the CA1 region of the dorsal hippocampus, whether the latest discovered serotonergic receptors, 5-HT5A, 5-HT6 and 5-HT7, are involved in the consolidation and reconsolidation of contextual fear conditioning (CFC) memory. For this, male rats with cannulae implanted in the CA1 region received immediately after the training or reactivation session, or 3h post-reactivation of the CFC, infusions of agonists or antagonists of the 5-HT5A, 5-HT6 and 5-HT7 receptors. After 24h, animals were subjected to a 3-min retention test. The results indicated that in the CA1 region of the hippocampus the 5-HT5A, 5-HT6 and 5-HT7 serotonin receptors participate in the reconsolidation of the CFC memory 3h post-reactivation. Additionally, the results suggest that the 5-HT6 and 5-HT7 receptors also participate in the consolidation of the CFC memory.

Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts.

OBJECTIVE: To examine the effects of asenapine on nitric oxide (NO) release and Ca(2+) transients in H9C2 cell line, which were either subjected to peroxidation or not. MATERIALS AND METHODS: H9C2 were treated with asenapine alone or in presence of intracellular kinase blockers, serotoninergic and dopaminergic antagonists, and voltage Ca(2+) channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca(2+) were measured through specific probes. RESULTS: In H9C2, asenapine differently modulated NO release and Ca(2+) movements depending on peroxidative condition. The Ca(2+) pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors, and voltage Ca(2+) channels blockers. CONCLUSIONS: On the basis of our findings, we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca(2+) homeostasis in H9C2; this would be of particular clinical relevance when considering their role in cardiac function modulation.