Abstract
BACKGROUND/OBJECTIVES: The dysregulation of the dopamine (DA) system is a key factor in neurodevelopmental and neurodegenerative disorders, including attention-deficit hyperactivity disorder (ADHD), Parkinson's disease, and schizophrenia. The habenula is a crucial regulator of DA neurotransmission and has been implicated in the pathophysiology of ADHD. Hizikia fusiformis (HF), a brown seaweed rich in fucoidan and fucosterol, has demonstrated neuroprotective properties. However, its effects on DA system modulation and neurodevelopmental disorders such as ADHD remain unclear. This study aimed to investigate the effect of HF extract on DA receptor expression in SH-SY5Y cells and its potential anti-ADHD effects in a neonatal habenula-lesioned (NHL) rat model exhibiting ADHD-like hyperlocomotion, inattention, and impulsivity. MATERIALS/METHODS: SH-SY5Y cells were treated with HF extracts at concentrations of 0.1, 1, and 10 μg/mL for 24 h, followed by immunostaining to evaluate DA-related protein expression. Male Sprague-Dawley rats were provided bilateral habenular injections of ibotenic acid (0.15 μL of 10 μg/μL in artificial cerebrospinal fluid) on postnatal day (PND) 7. HF extract was administered orally once daily from PND 21-28. Subsequently, behavioral assessments were conducted during the juvenile period (PND 28-35). RESULTS: HF treatment selectively downregulated dopamine receptor D (DRD)-2 and DRD5, whereas the levels of DRD1, DRD3, and DRD4 remained unchanged in SH-SY5Y cells. Behavioral analyses revealed that HF administration significantly ameliorated NHL-induced hyperactivity, attentional deficits, and impulsive behaviors in juvenile rats. CONCLUSION: These findings suggest that HF functions as a DRD2/DRD5 modulator, contributing to DA system regulation and potentially mediating anti-ADHD effects. Further studies are required to elucidate the mechanisms underlying the neuromodulatory effects of HF and its therapeutic potential for DA-related neuropsychiatric disorders.