Circling behavior and [14C]2-deoxyglucose mapping in rats: possible implications for autistic repetitive behaviors

Repetitive behaviors (such as circling) are one of the defining features of autism. The substantia nigra (SN) is involved in circling. We used unilateral SN pars reticulata (SNR) infusions of the GABA agonist muscimol to induce circling and deoxyglucose autoradiography mapping in adult and postnatal day (PN) 15 male and female rats to determine its substrates. In adults, muscimol infusions in posterior SNR induced a higher circling rate than in anterior SNR, after which males displayed faster circling than females. In contrast, PN15 female rats circled faster than PN15 male rats. Autoradiograms demonstrated age- and sex-specific alterations of deoxyglucose uptake in the SN pars compacta (SNC) associated with highest circling rates. The data suggest that there is a close relationship of the GABAergic SNR and dopaminergic SNC in the induction of circling; there is a topographic organization of the SNR in terms of circling behavior and associated deoxyglucose uptake, which is dependent on age and sex.