Age difference in apomorphine-induced stereotypy in rats: relationship to plasma and brain concentrations

Relationships between aging effects on apomorphine (AP)-induced stereotypy and AP concentrations in plasma and brain were studied in rats. In two separate behavioral studies, four groups of male Wistar rats (3, 6, 20, and 43 weeks of age) and two groups of female Wistar rats (5 and 35 weeks of age) were used, respectively: The former groups were administered 3 mg/kg AP SC and the latter 10 mg/kg AP SC. For the pharmacokinetic study, 5- and the 35-week female rats were injected with 10 mg/kg AP SC. In older rats, AP-induced stereotypy scores were less at the early stage of the observation period, and the onset of biting was slower and of longer duration. In 35-week rats, mean plasma AP concentrations were higher at 10--150 min and brain AP concentrations were lower at 5 and 10 min and higher at 30 and 90 min after injection. The longer duration of stereotypy in older rats seems to be due to the higher plasma or brain AP concentrations. The lower magnitude of stereotypy early after administration in older rats can be explained by the difference in brain AP concentrations, but cannot be fully explained by the difference in plasma levels only. It is suggested that other mechanisms, such as the decrease of dopaminergic binding sites, might also contribute to age differences in stereotypy.