Involvement of extracellular signal-regulated kinase (ERK) in the short and long-lasting antidepressant-like activity of NMDA receptor antagonists (zinc and Ro 25-6981) in the forced swim test in rats.
Short and long acting NMDA receptor (NMDAR) antagonists exert their antidepressant-like effects by activating signaling pathways involved in the synthesis of synaptic proteins and formation of new synaptic connections in the prefrontal cortex (PFC) of rats. The blockade of the ERK pathway abolishes ketamine and Ro 25-6981 antidepressant potency. However, the role of ERK in the antidepressant-like activity of short acting NMDAR antagonists is still unclear. More puzzling is the fact that the precise role of ERK in the short and long lasting effects of long-acting NMDAR antagonists is unknown. In this study, we show that zinc, (Zn) a short-acting NMDAR antagonist evokes only transient ERK activation, which is observed 7 min after its administration in the PFC of rats. In contrast to Zn, the long acting NMDAR antagonist Ro 25-6981 produces persistent ERK activation lasting up to 24 h. Pretreatment with the MAPK/ERK inhibitor (U0126) totally abolished Zn and Ro 25-6981 antidepressant-like activities in the forced swim test in rats. However, when U0126 is administered 15 min after Zn or Ro 25-6981 both compounds maintain their short-lasting antidepressant-like activity. On the other hand, posttreatment with U0126 significantly attenuated the long lasting antidepressant-like activity of Ro 25-6981. These results indicate that the activation of ERK is crucial for the short- and long lasting antidepressant-like activity observed in the FST in rats.
['Pochwat|Bartłomiej|B|', 'Rafało-Ulińska|Anna|A|', 'Domin|Helena|H|', 'Misztak|Paulina|P|', 'Nowak|Gabriel|G|', 'Szewczyk|Bernadeta|B|']
D000818:Animals D000928:Antidepressive Agents D001224:Aspartic Acid D002070:Butadienes D003866:Depressive Disorder D004195:Disease Models, Animal D004791:Enzyme Inhibitors D048049:Extracellular Signal-Regulated MAP Kinases D008297:Male D009043:Motor Activity D009570:Nitriles D009942:Organometallic Compounds D010636:Phenols D010766:Phosphorylation D010880:Piperidines D017397:Prefrontal Cortex D017207:Rats, Sprague-Dawley D016194:Receptors, N-Methyl-D-Aspartate D013574:Synaptosomes D013997:Time Factors D017967:Zinc Compounds
ERK NMDA Zinc Ro 25-6981 Depression