Effects of Melatonin on Behavioural Activities in Acetaminophen-induced Autism in Rat

Abstract

The present study aims to investigate the effect of acetaminophen in male rats after early postnatal exposure to acetaminophen on several behavioural alterations and its role to precipitate autistic-like behaviour with investigating the ameliorating role of melatonin on these parameters. Thirty healthy Albino male rat pups were used in this study. On a postnatal day 3 (PND3), the rat pups were divided into three groups (10 pups per group). Group1: As a control group, pups injected with normal saline for 7 days subcutaneously then administered with normal saline for 2 weeks orally. Group 2: pups injected acetaminophen subcutaneously in a dose (50mg/kg) once daily for 7 days, then these pups were administrated with normal saline for 2 weeks. Group 3: includes pups that were injected acetaminophen subcutaneously in a dose (50 mg/kg) once daily for 7 days then administrated with melatonin (10 mg/kg) for 2 weeks. Behavioural tests, such as nest seeking, were performed at PND 9; negative geotaxis test was done at "PND 15 and 17", an open field test was done at PND21. The present study demonstrated that acetaminophen exposed rat pups exhibited a significant difference in behavioural tests: nest seeking test showed that the pups of group 2 to approach the maternal bedding was (10.00±1.51) sec which was significantly higher than the time of the control group(4.50±2.19) sec. At PND15, the negative geotaxis test showed a significant increase in time spend to rotate 180° of the pups of group 2 (7.30±2.86) sec when compared with that of the control group (3.50±0.63)sec and melatonin treated group (4.56±0.63) sec. While at PND17, pups showed a significant increase in time spend to rotate 180° in negative geotaxis test in group 2 (7.40±2.90) sec compared with that of the control group (3.12 ±1.33) sec, and that of the melatonin treated group (4.18 ±1.43) sec. Data of open field test showed that pups of group 2 were traveled significantly more total distance (number of squares crossed) (31±8.34) compared to those traveled by pups of control (20±4.08) and melatonin treated groups (22±7.43). Administration of acetaminophen at dose 50 mg/kg from PND 3 to PND10 induces autistic-like behavioural manifested by several alterations in rat pups. These alterations were ameliorated by melatonin administration (10 mg/kg for 2 weeks) after exposure to acetaminophen.

Keywords

• acetaminophen
• autistic-like behaviour
• melatonin
• negative geotaxis
• open field test