Development of hypoglycemia and hyperglycemia as a function of number of trials in insulin conditioning

A neutral environment paired with insulin injections can develop the capacity to elicit glycemic changes. However, both conditioned hypoglycemia and conditioned hyperglycemia have been reported under apparently similar circumstances. The present study examined conditioned glycemic changes as a function of the number of conditioning trials and the novelty of the conditioning environment. Adult, male Wistar rats were injected with either insulin or physiological saline every second day, in either a novel or a familiar environment. On the test day, all rats were injected with saline and blood was collected 20 minutes later for determination of glucose levels. In rats given insulin in the novel environment, conditioned hypoglycemia was observed after two trials but was replaced by conditioned hyperglycemia after five trials. No conditioning at all occurred in the familiar environment. The two conditioned responses observed were interpreted as reflecting two unconditioned responses brought about by insulin--a hypoglycemic response to the central detection of insulin, and a hyperglycemic response to the detection of (insulin-induced) hypoglycemia. Taken in conjunction with previous experiments in which both conditioned response patterns have occurred, the present results suggest that the homeostatic response of hyperglycemia can become strong enough to overcome the initial conditioned response of hypoglycemia, but that its establishment depends on the use of a novel conditioned stimulus and a larger number of conditioning trials.