Theaflavin Attenuates Hyperactivity and Cognitive Deficits in a Rodent Model of Prenatal Alcohol-induced ADHD

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by persistent patterns of hyperactivity, inattention, and cognitive impairment. Prenatal alcohol exposure (PAE) has been identified as a significant environmental risk factor for ADHD, leading to structural and functional alterations in brain regions such as the striatum, and amygdala. Current pharmacological interventions for ADHD, while effective, are often associated with adverse effects and limited efficacy in addressing cognitive deficits. Theaflavin, a bioactive polyphenol in black tea, has shown neuroprotective potential. This study evaluates the potential of theaflavin to alleviate ADHD-like symptoms in a mouse model of prenatal alcohol exposure (PAE). Pregnant mice were administered alcohol 20mL/kg (10 mL/kg twice daily) from gestational day GD 7-16 to induce ADHD-like deficits in offspring. Following birth, male pups underwent an initial behavioral assessment on GD 22 to confirm ADHD-like symptoms using Y-maze, the open field test (OFT), and the marble burying test (MBT), after which they were allotted into five groups: control, ethanol- exposed (pathologic group), two theaflavin treatment groups (10 mg/kg and 20 mg/kg), and a positive control group receiving atomoxetine (1 mg/kg). After 30 days of treatment, a second behavioral assessment was conducted to ascertain the effect of the theaflavin. Histological evaluation of the striatum and amygdala was conducted to determine structural changes. Results indicated that theaflavin significantly improved behavioural deficits predictive of ADHD. There was an increase in percentage correct alternation, reduced arm entries as seen in the Y-maze. A significant decrease in duration of ambulation in the open field test, and decreased marble displacement in the marble burying test in a dose-dependent manner compared to the PAE group. Histological analysis revealed improved neuronal density in the striatum and amygdala of theaflavin-treated groups. Theaflavin mitigated neuronal damage exerting it’s neuroprotective effects highlighting its potential as a therapeutic candidate for ADHD management.