Abstract

Bilateral lesions in the frontal cortex (FC), posterior cortex (PC), or caudate nucleus were created in rats. Responsiveness to amphetamine was tested over a period of 5 to 6 months in operated and control animals. The results may be summarized as follows:

1. An increased sensitivity to amphetamine, as indicated by changes in spontaneous locomotor activity, was observed in rats with FC or PC ablations. No change in sensitivity to the drug was seen in rats with lesions in the caudate nucleus.

2. Changes in sensitivity to amphetamine were not related to changes in weight or spontaneous locomotor activity.

3. There was no relationship between the amount of cortex destroyed and the changes in sensitivity to amphetamine.

4. In the case of the FC group, the emergence of the change in responsiveness to amphetamine was gradual, an asymptote not being reached for about 4 weeks postoperatively. Following PC ablations, an immediate rise in sensitivity to the effects of the drug was noted. This change diminished for about 3 weeks, after which a second rise was seen, paralleling the changes noted in the FC group.

5. The increased responsiveness to amphetamine which was observed in both the FC and the PC groups was maintained for the duration of the study.

6. Results are discussed in terms of several possible explanations: a) denervation supersensitivity; b) infringement by the lesion on specific receptor sites for the drug; c) infringement by the lesion on an area remote from the site of action of the drug, which normally modulates the overall effect of the drug; d) alterations in the blood-brain barrier as the result of the brain lesions.