Avoidance responding following amphetamine-induced dopamine depletion.

The effect of an amphetamine-induced depletion of striatal dopamine on active and passive avoidance responding of rats was examined. Sixteen animals received two sets of 4 injections each of 15 mg/kg d-amphetamine, administered at 2 hr intervals with each set delivered one week apart. One week after the last injection, animals were given 50 consecutive active avoidance trials in a shuttle box. Animals treated with amphetamine exhibited a 50% depletion of striatal dopamine and showed a slower learning curve, as evidenced by significantly fewer avoidances and a slower escape latency during trials 21-30. Both groups demonstrated a 90% avoidance rate by trials 41-50. A separate group of rats was treated as above and trained for several weeks on the active avoidance procedure. Haloperidol (0.01-0.10 mg/kg intraperitoneally) dose-dependently decreased avoidance number and increased avoidance and escape latency in both groups, an effect that was exaggerated in those animals previously treated with amphetamine. Finally, these animals were tested in the same apparatus using a passive avoidance procedure. The amphetamine treatment produced a significantly higher mean number of avoidances in this procedure compared to saline-treated animals during trials 1-20. These results suggest that the impairment in conditioned avoidance following amphetamine treatment is due to a motoric, rather than a cognitive deficit.