THE EFFECTS OF MELATONIN ADMINISTRATION AND CURIOSITY ACTIVATION ON DOPAMINE AND DOPAMINE TRANSPORTER EXPRESSION IN THE LIMBIC SYSTEM OF D-GALACTOSE-INDUCED AGING RAT MODEL

Age‑related reductions in dopamine levels and dopamine transporter (DAT) expression within the limbic system are associated with cognitive decline, motivational deficits, and reduced neuroplasticity. Melatonin, a neurohormone involved in circadian rhythm regulation, has been shown to mitigate age-related neurodegeneration. In parallel, curiosity, an intrinsic cognitive‑motivational state driven by information seeking, activates the limbic dopaminergic reward system and may enhance dopamine signaling through sustained neural stimulation. Therefore, this study investigated the effects of melatonin administration and curiosity activation on dopamine-related markers in the nucleus accumbens (NAc) and hippocampus of D-galactose-induced aging rats. Rats were randomly assigned to five groups: control, D‑galactose (150 mg/kg), D‑galactose plus melatonin (10 mg/kg), D‑galactose plus curiosity activation, and D‑galactose plus melatonin and curiosity activation. Treatments were administered once daily for eight weeks. Curiosity activation was induced using the radial arm maze and novel object recognition tests. Tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis, and DAT expression were assessed by immunohistochemistry. The results showed that TH and DAT expression in the NAc and hippocampus were decreased in the D‑galactose group compared with controls. Melatonin, curiosity activation, and their combination attenuated these reductions compared with the D‑galactose group. These findings suggest that melatonin and curiosity‑related behavioral activation exert neuroprotective effects on dopaminergic regulation in the limbic system during brain aging.
Acknowledgement: This study was supported by research grant from HRH Princess Mahachakri Sirindhorn Medical Center, Faculty of Medicine, Srinakharinwirot University (Contract No.555/2568).