Acute intrahippocampal administration of melanin-concentrating hormone impairs memory consolidation and decreases the expression of MCHR-1 and TrkB receptors

Interest in the role of melanin-concentrating hormone (MCH) in memory processes has increased in recent years, with some studies reporting memory-enhancing effects, while others report deleterious effects. Due to these discrepancies, this study seeks to provide new evidence about the role of MCH in memory consolidation and its relation with BDNF/TrkB system. To this end, in the first experiment, increased doses of MCH were acutely administered in both hippocampi to groups of male rats (25, 50, 200, and 500 ng). Microinjections were carried out immediately after finishing the sample trial of two hippocampal-dependent behavioral tasks: the Novel Object Recognition Test (NORT) and the modified Elevated Plus Maze (mEPM) test. Results indicated that a dose of 200 ng of MCH or higher impaired memory consolidation in both tasks. A second experiment was performed in which a dose of 200 ng of MCH was administered alone or co-administered with the MCHR-1 antagonist ATC0175 at the end of the sample trial in the NORT. Results showed that MCH impaired memory consolidation, while the co-administration with ATC-0175 reverted this detrimental effect. Moreover, MCH induced a significant decrease in hippocampal MCHR-1 and TrkB expression with no modification in the expression of BDNF and NMDA receptor subunits NR1, NR2A, and NR2B. These results suggest that MCH in vivo elicits pro-amnesic effects in the rat hippocampus by decreasing the availability of its receptor and TrkB receptors, thus linking both endogenous systems to memory processes.

Automated summary

Interest in the role of melanin-concentrating hormone (MCH) in memory processes has grown, but studies have provided contradictory findings. This study investigated the effects of MCH on memory consolidation and the BDNF/TrkB system. The results showed that high doses of MCH impaired memory consolidation, but this effect could be reversed by a co-administration with the MCHR-1 antagonist ATC-0175. Additionally, MCH decreased the expression of MCHR-1 and TrkB, linking both endogenous systems to memory processes.