Modeling Symptoms of Attention-Deficit Hyperactivity Disorder in a Rat Model of Fetal Alcohol Syndrome

Abstract

Aims: Several studies indicate the similarity between the symptoms of fetal alcohol syndrome and attention-deficit hyperactivity disorder (ADHD). This study hypothesized that prenatal exposure to ethanol (EtOH) can be used as an animal model of ADHD in Wistar rats. Methods: At the first stage of the study, alcohol was delivered to the pregnant dams (237–252 g) by intra-gastric route throughout Gestation Days 8–20 at a dose of 6 g/kg/day. Untreated control group with isocaloric sucrose intubation was also included. Of the 16 male pups (174–180 g), 8 were in the fetal alcohol effects (FAE) group and 8 were in the untreated control group. Subjects went through behavior shaping, discrimination learning and reversal learning. Number of sessions to learn the tasks, response frequency to inhibitory (S−) and excitatory (S+) stimulus features, response latency and inter-response time (IRT) were measured. Results: Significant differences were obtained on only the reversal task. Rats with FAE needed greater number of sessions to learn the reversal task, and they had a higher frequency of incorrect responses in specifically the latter part of the sessions. Conclusion: Our results suggest that reversal learning of FAE rats exhibits deficit in the inhibition of pre-learned responses. Responses behaviorally mimicked attention deficit and impulsivity symptoms of human ADHD. However, the experimental design of the study was not conducive to hyperactivity. Accordingly, rats with FEA can be an alternative to other models since it is not, for example, based on a symptom that is atypical (such as hypertension) to ADHD. Short Summary: Significant difference was obtained in a reversal task between male rats prenatally exposed to ethanol and matched controls. The greater number of sessions for learning and higher frequency of incorrect responses behaviorally mimicked symptoms of ADHD, suggesting that rats with fetal ethanol effects can serve as a useful animal model.