EFFECTS OF IRREVERSIBLE DOPAMINE RECEPTOR INACTIVATION ON LOCOMOTOR-ACTIVITY AND GROOMING IN THE 17-DAY-OLD AND 90-DAY-OLD RAT

Ontogenetic differences in the behavioral recovery of R(-)-propylnorapomorphine (NPA) treated rats were assessed following irreversible DA receptor antagonism by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). In the first two experiments, 17- and 90-day-old rats were given EEDQ (7.5 or 15.0 mg/kg, IP) or vehicle after half the rats were initially treated with the selective DA D-1 and D-2 antagonists SCH 23390 and sulpiride. (The sulpiride/SCH 23390 treatment protects DA receptors from EEDQ-induced inactivation.) NPA's (0.1 or 1.0 mg/kg) effects on locomotor activity and grooming were assessed 1, 2, 4 and 8 days after the EEDQ pretreatment. In a third experiment, the effects of habituating the 17- and 90-day-old rats to the testing chamber were assessed 1, 2 and 4 days after EEDQ pretreatment. In this experiment, some groups received successive treatments of saline or NPA prior to behavioral testing. To assess the possible effects of drug-sensitization other groups received saline on days 1 and 2 and NPA on day 4. In 90-day-old rats, EEDQ eliminated, for up to 4 days, the ability of NPA to enhance locomotor activity and depress grooming. Prior treatment with DA antagonist drugs was sufficient to protect DA receptors from EEDQ-induced inactivation, since these groups exhibited normal behavioral responses after challenge with NPA. In contrast, EEDQ did not eliminate, and may have enhanced, NPA's effects on the locomotor activity and grooming of 17-day-old rat pups. Habituating the rats to the testing chamber decreased the locomotor activity of the mature rats, but not the 17-day-old rat pups. Drug sensitization did affect locomotor activity, but could not account for the behavioral recovery exhibited by the mature rats and pups. These results indicate that the behavioral effects of EEDQ differ dramatically in young rats compared to adults. The neurochemical bases for these ontogenetic differences remain unknown.