INCREASED FIXED-RATIO PERFORMANCE AND DIFFERENTIAL d-AND l-AMPHETAMINE ACTION FOLLOWING NOREPINEPHRINE DEPLETION BY INTRAVENTRICULAR 6-HYDROXYDOPAMINE

¹ Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota

The intraventricular injection of 200 µg of 6-hydroxydopamine (6-OHDA) into rats trained to respond on a fixed-ratio 30 (FR 30) schedule of food reinforcement resulted in decreased response rates which returned to predrug rates after 8 days. The response rates then gradually increased and remained significantly greater for up to 156 days after the 6-OHDA treatment. Vehicle-injected control animals did not change their rates over this same period of time. While the 6-OHDA treatment did increase reinforced responding, it did not increase the number of unreinforced (extinction) responses or exploratory activity. The dose of 6-OHDA used depleted hypothalamic and midbrain-striatal norepinephrine (NE) measured 1 week later, but midbrain-striatal dopamine was unchanged. At the end of the behavioral study, 5 months later, NE levels had partially recovered and the extent of this recovery was positively correlated with the increased response rates. The suppression of the FR responding by d-amphetamine was not altered by the 6-OHDA treatment. When l-amphetamine was given to the same rats, the behavioral suppression was significantly attenuated in the group that had received 6-OHDA. These results suggest a relatively greater importance of NE in some of the operant behavioral actions of l-amphetamine than of d-amphetamine.