Impaired acquisition of an operant response in young rats depleted of brain dopamine in neonatal life.

In an attempt to examine the ability of brain dopamine (DA) depletion to alter learning ability in the developing rat, the rate of acquisition of a positively reinforced lever pressing response was examined in rats during days 30-45 of life following treatment with desmethylimipramine (DMI, 20 mg/kg IP) and 6-hydroxydopamine (6-OHDA, 35 micrograms intraventricularly) at 3 and 6 days of age, respectively. The 6-OHDA treatment produced a 40%-70% reduction of brain DA without altering growth rate, water intake, or locomotor activity. On the average, water-deprived control rats achieved the criterion for acquisition (50 reinforced lever presses/h) on a fixed-ratio 1 schedule of water reinforcement after 3.1 +/- 0.5 sessions (mean +/- SEM). In contrast, nearly one-fourth of the DMI + 6-OHDA-treated rats failed to acquire the response after 16 sessions and the remaining 6-OHDA-treated rats required more than twice as long as controls for acquisition (7.8 +/- 0.7 sessions). These results suggest that brain DA depletion in neonatal life can impair the acquisition of an operant response during development and that this deficit is independent of changes in growth rate or locomotor activity.