Effects of Intraventricular 6-Hydroxydopamine and Replacement Therapy with Norepinephrine, Dopamine, and Serotonin on Self-Stimulation in Diencephalic and Mesencephalic Regions in the Rat

Although 6-hydroxydopamine (6-OHDA) reduced the rate of hypothalamic self-stimulation, it is not known whether the same effect is produced at other reinforcing sites remote from the hypothalamus. This was investigated in rats implanted with rewarding probes in the hypothalamus, in the substantia nigra, in the midbrain, and in the pontine region. Two patterns of self-stimulation emerged in each subject. One, characterized by short, medium and long-stimulus-train durations, was seen in the hypothalamus, in the substantia nigra, and in selected sites in the pons. The other, which comprised only short stimulus-trains, was found in the medial midbrain and in the pontine region. 6-OHDA (250 mug intraventricular route) reduced the rate of responding in the regions where responding was for short, medium, and long stimulus trains. It has a minor effect on responding in regions where the brain rewards were exclusively of short duration. Thus, self-stimulation in the hypothalamus, in the substantia nigra and in the pons was suppressed after 6-OHDA, while self-stimulation in the medial midbrain and at sites in the pons, where selection was for short trains, was only slightly below control levels after 6-OHDA. L-Norepinephrine (L-NE) (10, 20 and 30 mug) injected into the lateral ventricle of the 6-OHDA-treated rats temporarily reinstated self-stimulation in the lateral hypothalamus but not in the substantia nigra and not in the pontine region where the pattern of selection had been for long brain rewards. Dopamine (DA) was not effective as an antagonist of the suppressant action of 6-OHDA. Serotonin (5-HT) reinstated self-stimulation behavior in the lateral hypothalamus but not in the other positive regions. Its action was less than that of NE and did not take place in all animals tested.