Effects of dopamine D 1 and D 2 receptor antagonists on cocaine-induced place preference conditioning in preweanling rats

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The effects of dopamine D 1 and D 2 receptor antagonists on the reward processes of 10- and 17-day-old rats were assessed using the conditioned place preference paradigm. Conditioning and testing were conducted in a three-compartment chamber, with each end compartment having its own distinct tactile and odor cues (almond and lemon). During six experiments, 10- and 17-day-old rats (age at initial conditioning) were injected intraperitoneally with either saline, the dopamine D 1 receptor antagonist R(±)-SCH 23390 hydrochloride (0.01–1.0 mg/kg), or the dopamine D 2 receptor antagonists (±)-sulpiride (1–100 mg/kg) or S(-)-eticlopride hydrochloride (0.1–0.5 mg/kg) 30 min prior to being injected with cocaine hydrochloride (20 mg/kg) or saline. After the latter injections, rats were immediately confined in the lemon-scented (nonpreferred) compartment for 30 min. On the alternate conditioning day, rats were injected with saline and confined in the almond-scented compartment. On the third day (i.e., the test day), rats were given saline and allowed free access to the entire chamber for 15 min. The results showed that the dopamine D 1 receptor antagonist SCH 23390 blocked the cocaine-induced place preference conditioning of both 10- and 17-day-old rats. Surprisingly, the dopamine D 2 receptor antagonists sulpiride and eticlopride blocked the place preference conditioning of 10-day-old rats, while leaving the 17-day-old rats unaffected. These results indicate that dopamine D 1 receptors are critically involved in the reward processes of preweanling rats, but that the importance of dopamine D 2 receptors changes across ontogeny.