Amphetamine reverses learning deficits in 6-hydroxydopamine-treated rat pups

At 5 days of age, rat pups were treated with a combination of desmethylimipramine (DMI) and 6-hydroxydopamine (6-OHDA) to selectively deplete brain dopamine (DA) or with vehicle (saline) control solutions. Two days later, all animals received conditioning to a novel odor by pairing the odor with intraoral milk. When the odor was anise, treated pups spent less time near the conditioned stimulus than did controls, but there were no 6-OHDA effects when the stimulus was a lemon odor (Experiment I). The difference in performance between the treated and control animals was not attributable to alterations in activating effects of the reinforcer (Experiment I), changes in olfactory sensitivity or olfactory preference (Experiment II), or sensitization to the stimulus (Experiment III). In Experiment IV, animals received d-amphetamine sulfate (0.5 mg/kg) prior to conditioning, testing, or both conditioning and testing. Amphetamine treatment before conditioning produced an improvement in performance in animals previously treated with 6-OHDA/DMI, but it impaired performance in controls, regardless of the time of injection. The results indicate a role of brain DA in learning in young rats.