Scopoletin and rutin attenuate ethanol reward in mouse-conditioned place preference test

Abstract

Introduction: In Traditional Chinese Medicine (TCM), Morinda citrifolia Linn. (Hai ba ji), is utilized for its various parts such as leaves, fruits, flowers, roots, and bark, serving as a tonic and addressing ailments including fever, skin, eye, throat, and gum issues, as well as nausea, vomiting, and neurological diseases. Previous research indicated that M. citrifolia Linn. fruit and its juice reduced ethanol-conditioned place preference (CPP) in mice, with scopoletin (SCOP) and rutin (RUT) proposed as the main bioactive compounds responsible for this effect. This study aimed to evaluate the impact of SCOP and RUT on ethanol reward using the CPP test in mice. Methods: The CPP protocol consisted of a habituation phase spanning 3 days, a 1-day preconditioning phase, 10 days of conditioning, a rest day, and a post-conditioning day. The vehicle-saline control and vehicle-ethanol control groups received oral administration of a 1 % w/v solution of sodium carboxymethyl cellulose (CMC) at a dosage of 10 ml/kg. SCOP and RUT were administered orally at doses ranging from 0.05 to 1 mg/kg body weight (bw), while acamprosate (ACAM) was administered at a dosage of 300 mg/kg bw, all one hour before postconditioning. Statistical analyses utilized both repeated measures two-way and one-way ANOVA. Results: Oral administration of SCOP (0.05, 0.1, and 0.5 mg/kg bw) and RUT (0.05 mg/kg bw) one hour before postconditioning testing on day 16 markedly reduced ethanol CPP in mice. Additionally, SCOP and RUT at all tested doses (0.05–1 mg/kg bw, p.o.) did not induce any changes in normal locomotor activity in mice. Discussion: These results suggest that SCOP and RUT diminish ethanol reward in mice, underscoring the therapeutic potential of these phytochemicals in managing alcohol use disorder.

Keywords

• Alcohol use disorder
• Conditioned place preference
• Locomotor activity
• Noni
• Rutin
• Scopoletin