The role of genetic and early environmental factors in determining apomorphine susceptibility

Rationale: There is ample evidence that rats show large individual differen ces in their response to dopaminergic drugs, such as apomorphine. Objective : The aim of the present study was to investigate the role of genetic and ( early) environmental factors in determining the adult susceptibility to apo morphine. Four experiments were performed: In experiment 1, the original se lective breeding of rats for apomorphine susceptibility (leading to APO-SUS and APO-UNSUS rats) was extended and replicated in an independent group of Wistar rats. In experiment 2, APO-SUS males were cross-bred with APO-UNSUS females and vice versa. In experiment 3 APO-SUS litters were cross-fostere d to APO-UNSUS mothers or infostered to unknown APO-SUS mothers and vice ve rsa. In experiment 4 APO-SUS and APO-UNSUS rats were maternally deprived on postnatal day 9, for a single 24-h period. Methods: Adult rats were subcut aneously injected with 1.5 mg/kg apomorphine and their gnawing response was automatically recorded in a gnawing box for 45 min. Results: In experiment I, the original breeding was extended up to generation 24, leading to a st rong and consistent difference in gnawing scores. The replication experimen t also succeeded in differentiating APO-SUS and APO-UNSUS. The cross breedi ng experiments showed that the APO-SUS/UNSUS offspring showed gnawing score s in between the original selection lines. Cross-fostering APO-SUS with APO -UNSUS significantly reduced the gnawing response in the offspring, whereas it did not affect the gnawing score in the APO-UNSUS animals. Maternal dep rivation had the opposite effect: increase in gnawing response in APO-UNSUS , with no effect in APO-SUS. Conclusion: The results show a clear-cut contr ibution of both genetic and early environmental factors to the susceptibili ty of apomorphine.