Structure and function in the developing brain: Effects of early frontal and cerebellar lesions on activity, learning, social and emotional behavior in the rat

Autism, characterized by disrupted social interaction and communication skills, and Attention Deficit Hyperactivity Disorder (ADHD), characterized by hyperactivity and inattention, are two neurodevelopmental disorders that have recently been linked to common dysfunctions in the frontal lobes and cerebellum. The present study was designed to evaluate the neonatal rat as an animal model for neurodevelopmental disorders. The behavior of rats with early Frontal (FR), Cerebellar (CB), or Frontal + Cerebellar (FR + CB) lesions, performed at either Post-natal Day 2 (PD 2) or 9 (PD 9), was evaluated with regard to activity, learning, social, and emotional behavior between the age of 3--31 days. In Experiment 1, 3 and 10-day-old pups were tested on their ability to habituate to a novel odor. FR lesions increased activity in 3-days-olds while CB, and FR + CB lesions disrupted odor habituation learning in 10-day-olds. In Experiment 2, 17-day-old pups were evaluated on activity in the open-field and ability to habituate to a novel environment. FR lesions resulted in increased locomotor activity while CB lesions resulted in increased grooming, a stereotypical behavior. Pups with PD 9 CB lesions also failed to habituate to the novel environment of the open-field. In Experiment 3, 24-day-old juveniles were evaluated on social behavior in the play test, as measured by frequency of pinning behavior. FR lesions increased levels of play behavior while CB lesions decreased play. In Experiment 4, 31-day-old juveniles were evaluated on emotionality in the elevated plus maze as measured by the number of distal open arms entries. Rats with CB lesions made twice as many distal open arm entries relative to the other lesioned groups; however, this result did not reach statistical significance. In conclusion, the results of the present study suggest that the effects of early frontal and cerebellar lesions can be dissociated on several different behavioral measures in young rats. Furthermore, neonatal rats with frontal and cerebellar lesions exhibit several behaviors during ontogeny that mimic those seen in children with ADHD and autism, such as hyperactivity and disrupted social interaction. The neonatal rat may thus prove to be a useful animal model for childhood neurodevelopmental disorders.