Further analysis of the resistance of the diabetic rat to d-amphetamine.

Rats that were made diabetic by the subcutaneous injection of alloxan monohydrate were found to be resistant to the anorexic action of d-amphetamine. This resistance to amphetamine anorexia did not appear attributable to an increased hunger motivation of the diabetic rats, but rather seemed due to a diminished action of the drug in alloxan-injected animals. This conclusion was supported by further experiments indicating that alloxan-injected rats show diminished locomotor activity and stereotyped behavior following amphetamine administration. Furthermore, the amphetamine resistance appears to be the result of the diabetic state, since amphetamine-induced stereotyped behavior could be reinstated in alloxan-injected rats by the administration of protamine zinc insulin for ten days. The results of these investigations suggest that there exists an altered central nervous system response to d-amphetamine in the diabetic rat. These possibility of an abnormal functioning of central catecholamine-containing neurons in such animals is discussed.