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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 ATC-0175 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.

Rats were randomly assigned to enriched (EE) or standard environments (SE) at 21 or 73 days of age, for 17 days. Half of the rats of each rearing condition were trained in a radial maze (RM). At 38 days (pre-pubertal) or 90 days (young), rats were sacrificed and brain cytosolic and mitochondrial nitric oxide synthase (mtNOS) activity was assayed. Western blot analysis of brain mtNOS was conducted. In the pre-pubertal group, EE rats improved their performance in the RM while SE rats did not. In the young group, SE and EE rats showed a random performance in the RM. In SE pre-pubertal rats, training increased brain cytosolic NOS and mtNOS activity by 68% and 82%. In EE non-trained pre-pubertal rats, brain cytosolic NOS and mtNOS activity increased by 80% and 60%, as compared with SE non-trained pre-pubertal rats. In EE pre-pubertal rats that were trained, brain cytosolic NOS and mtNOS activity increased by 70% and 90%, as compared with SE pre-pubertal rats that were not trained. A higher protein expression of brain mtNOS was found in EE rats, as compared with SE animals. Mitochondrial complex I activity was higher in EE than in SE rats. Training had no effect on complex I activity neither in SE nor in EE rats. In young rats, no significant differences in enzyme activities were found between EE and SE rats. These results support the hypothesis that brief exposure to EE and training produce effects on behavioral performance and on biochemical parameters in an age-dependent manner.