Ontogenetic effects of EEDQ on amphetamine-induced behaviors of rats: role of presynaptic processes.

Previous research has shown that the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) affects dopamine (DA) synthesis and metabolism in both preweanling and adult rats. In the present study, we attempted to determine the behavioral relevance of EEDQ's presynaptic actions. To that end, 17- and 90-day-old rats were injected with either EEDQ (7.5 mg/kg, IP) or its vehicle 30 min after half the rats were pretreated with the selective DA antagonists SCH 23390 and sulpiride. (SCH 23390/sulpiride pretreatment was used to protect D1 and D2 receptors from EEDQ-induced inactivation.) The behavioral effects of amphetamine (0, 0.1, 0.3 or 1.0 mg/kg, IP) were then assessed 1, 2, 4, and 8 days after EEDQ treatment. Amphetamine-induced behaviors were used to assess EEDQ's presynaptic actions, because amphetamine does not directly bind to the DA receptor, but rather releases DA from the presynaptic terminal. Further, since half of the EEDQ-treated rats had a full complement of DA receptors (i.e., those rats pretreated with SCH 23390/sulpiride), EEDQ's actions in the presynaptic terminal could be dissociated from actions at pre- and postsynaptic receptors. In general, the results showed that EEDQ blocked most of the amphetamine-induced behaviors of both 17- and 90-day-old rats. Surprisingly, pretreatment with SCH 23390 and sulpiride only protected the amphetamine-induced behaviors of adult rats, but not the behaviors of 17-day-old rat pups. When considered together, these results suggest that EEDQ's presynaptic effects are not behaviorally relevant to the adult rat, but may be responsible for eliminating amphetamine-induced behaviors in the 17-day-old rat pup.