Antidepressant- and Anxiolytic-like Effects of Nicotinamide in a Chronic Unpredictable Mild Stress Mouse Model

Depression and anxiety are common stress-related neuropsychiatric disorders associated with impaired  neuroplasticity, oxidative stress, neuroinflammation, and altered cellular energy metabolism. Nicotinamide, a  precursor of nicotinamide adenine dinucleotide (NAD?), has emerged as a potential neuroprotective agent,  although its behavioral effects in chronic stress models remain incompletely characterized. This study investigated  the antidepressant- and anxiolytic-like effects of nicotinamide in mice exposed to chronic unpredictable mild  stress (CUMS). Thirty adult Swiss albino mice were allocated to six groups: distilled water control, CUMS,  fluoxetine (20 mg/kg), and nicotinamide-treated groups (100, 200, and 400 mg/kg). Following CUMS induction,  behavioral assessments were performed using the forced swim test (FST), open field test (OFT), and elevated plus  maze (EPM). CUMS significantly increased immobility time in the FST, confirming the induction of depressive like behavior. Nicotinamide at 200 and 400 mg/kg significantly reduced immobility time compared with untreated  CUMS mice, indicating antidepressant-like activity. In the OFT, nicotinamide reduced urination and defecation  frequencies at all doses, while the 200 mg/kg dose significantly increased rearing behavior, suggesting partial  attenuation of anxiety-related emotionality. However, nicotinamide did not significantly alter center crossing  frequency or any EPM parameter. These findings demonstrate that nicotinamide exerts significant antidepressant like effects and modest anxiolytic-like effects in CUMS-exposed mice. The antidepressant-like actions of  nicotinamide may be mediated through NAD?-dependent metabolic, neuroplastic, anti-inflammatory, and  oxidative stress-related pathways. Further mechanistic studies are required to elucidate the molecular basis of  these behavioral effects.

Key Words: Nicotinamide, chronic unpredictable mild stress, depression, anxiety, NAD?