Ontogenetic differences in the effects of EEDQ on dopamine-mediated behaviors.

Previous results suggest that 17-day-old rat pups may have substantial reserves of both D1 and D2 receptors. To assess this possibility, the behavioral effects of a nonselective dopamine (DA) agonist, R-propylnorapomorphine (NPA), were measured in 11- and 17-day-old rat pups previously treated with the irreversible DA receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Rat pups were treated with EEDQ (7.5 mg/kg) either alone or in combination with the D1 and D2 antagonists, SCH 23390 (1.0 mg/kg) and sulpiride (100 mg/kg), respectively. (The SCH 23390 and sulpiride were used to protect dopamine receptors from EEDQ-induced inactivation.) NPA's effects on stereotyped sniffing and locomotor activity were then assessed 1, 2, and 4 days after EEDQ pretreatment. Results showed that NPA (0.01, 0.1, 1.0, or 5.0 mg/kg) produced a dose-dependent increase in the stereotyped sniffing of both aged rats. Unexpectedly, however, EEDQ did not disrupt the NPA-induced stereotyped sniffing of either the 11- or 17-day-old rat pups. Thus a behavior (i.e., stereotyped sniffing) that requires the activation of a large complement of DA receptors was not sensitive to the receptor-depleting actions of EEDQ. Moreover, the behaviors of 11-day-old rats, which have fewer DA receptors than older pups or adults, were also not susceptible to the effects of EEDQ. When taken together, these results suggest that EEDQ's inability to block the agonist-induced behaviors of preweanling rat pups cannot be explained by ontogenetic changes in DA receptor reserves.