Discrimination of insulin-produced hypoglycemia in rats

Abstract

Hypoglycemia is an abnormal state that can be induced by administering insulin to a fasting animal. Rats were trained to discriminate the normal state of euglycemia from the hypoglycemia produced by injection of 6 units/kg insulin. A drug discrimination procedure was used with a two-lever operant response. Insulin or water injected 25 min prior to the operant sessions determined whether left or right lever presses were reinforced. During 40 training sessions, reliable discrimination of the insulin-produced cue developed. After insulin injection, mean blood glucose levels dropped to about 75% of preinjection values. At 12 min postinsulin injection, prior to the development of hypoglycemia, noninsulin responses were made. Noninsulin responses were also made after injection with 800 mg/kg ethanol, indicating that a novel interoceptive state did not substitute for the insulin-produced cue. Insulin injections produced less severe hypoglycemia in less food-deprived rats, which again gave noninsulin responses. Animals can be trained to recognize the insulin-produced state, which presumably involves hypoglycemia, and/or counterregulatory process evoked in response to the drop in blood glucose.