The role of genetic and early environmental factors in determining apomorphine susceptibility.
BACKGROUND
There is ample evidence that rats show large individual differences 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 apomorphine. Four experiments were performed: In experiment 1, the original selective 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-fostered to APO-UNSUS mothers or infostered to unknown APO-SUS mothers and vice versa. 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 subcutaneously injected with 1.5 mg/kg apomorphine and their gnawing response was automatically recorded in a gnawing box for 45 min.


RESULTS
In experiment 1, the original breeding was extended up to generation 24, leading to a strong and consistent difference in gnawing scores. The replication experiment also succeeded in differentiating APO-SUS and APO-UNSUS. The cross breeding experiments showed that the APO-SUS/UNSUS offspring showed gnawing scores 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 deprivation had the opposite effect: increase in gnawing response in APO-UNSUS, with no effect in APO-SUS.


CONCLUSIONS
The results show a clear-cut contribution of both genetic and early environmental factors to the susceptibility of apomorphine.
Ellenbroek
B A
BA
Department of Psychoneuropharmacology, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. A.Ellebroek@pnf.kun.nl
Sluyter
F
F
Cools
A R
AR
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001947:Breeding; D003433:Crosses, Genetic; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D005260:Female; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000235:genetics; D008426:Maternal Deprivation; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012641:Selection, Genetic; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology*
D001058:Apomorphine