Resistance of alloxan-diabetic rats to the behavioral activation induced by d-amphetamine: partial restoration with a high fat/protein diet

Rats which were diabetic following the subcutaneous injection of alloxan monohydrate have been found to be resistant to the locomotor stimulant and stereotypy inducing actions of d-amphetamine. By using behavioral ratings to assess the effect of amphetamine, the resistance of the diabetic rat has been found modifiable by dietary manipulation. Whereas alloxan-injected rats maintained on a high carbohydrate diet (Purina powder) show predominantly increased forward locomotion and weak stereotyped sniffing following 2.0 mg/kg d-amphetamine sulfate, this same dose typically induces moderately intense stereotyped sniffing in alloxan-injected rats which have ingested a high/fat protein diet for 6 weeks. The strength of the behavioral activation produced by d-amphetamine in non-diabetic control rats (1) is not influenced by whether they ingest a high carbohydrate or high fat/protein diet, and (2) is significantly greater than the behavioral activation seen in diabetics maintained on high carbohydrate diet, but (3) does not differ significantly from the degree of behavioral activation seen in diabetic rats maintained for 6 weeks on a high fat/protein diet. Thus, it appears that the ingestion of a high fat/protein food source largely restores the diabetic rat's behavioral response to this dose of amphetamine. Because the ingestion of a high fat/protein diet ameliorates the hyperglycemia and hyperdipsia and facilitates the weight gain of the diabetic animal, it is suggested that this diet restores the responsiveness of alloxan-injected rats to d-amphetamine by partially correcting the metabolic deficiencies associated with the diabetic state.