To evaluate the effects of short- and long-term melatonin (MLT) supplementation in young rats on behavioral and biochemical parameters related to mood, cognition, and mitochondrial function in adulthood.

Melatonin modulates circadian rhythms and neuronal activity through receptors in the hippocampus, particularly in the CA1 and CA3 regions. It can influence synaptic transmission and long-term potentiation, both essential for memory processing. However, the long-term impact of early melatonin exposure on adult behavior and hippocampal bioenergetics remains unclear. Understanding these effects is crucial to determine the safety of chronic melatonin use during development.

Forty-three male Wistar rats (250–350 g) were randomly assigned to three groups: saline + saline (n = 13), MLT short-term (n = 15), and MLT long-term (n = 15). Behavioral tests evaluated anxiety-, depression-, and memory-related parameters. Biochemical assays measured the activity of mitochondrial respiratory chain complexes in hippocampal tissue. All experimental procedures were approved by the institutional Animal Ethics Committee and conducted in accordance with international guidelines for animal research.

Short-term melatonin exposure induced depressive-like behavior and reduced locomotor activity. Conversely, long-term treatment increased social interaction, decreased anxiety-like behavior, and improved learning and memory performance. Biochemical analyses revealed enhanced activity of mitochondrial complex II in the hippocampus after prolonged melatonin exposure, suggesting improved mitochondrial efficiency and potential adaptive effects.

Prolonged melatonin supplementation improved memory and hippocampal mitochondrial function without consistent adverse behavioral outcomes. These findings suggest possible neuroprotective properties of long-term melatonin use. Nevertheless, further studies are warranted to assess its systemic effects and long-term safety. Understanding melatonin’s role in neuroprotection may guide the development of safe and effective therapeutic analogues.