Classically conditioned responses following repeated insulin and glucose administration in humans

This paper describes the neural basis and the role of Pavlovian conditionin g in the modification of blood glucose and related endocrine parameters aft er repeated insulin and glucose administration. Pavlovian conditioning requ ires that conditioned stimulus (CS) and unconditioned stimulus (US) are bot h detected in the central nervous system (CNS), where the CS-US association takes place. We will therefore elucidate the detectability of insulin and glucose in the CNS. Since current data focus almost exclusively on animals, we conducted a placebo-controlled insulin conditioning experiment in human s (Experiment 1). Compared with the control group with CS-placebo pairings throughout, the experimental group with previous CS-insulin pairings in the acquisition phase showed a conditioned decrease in blood glucose and a tre nd for a conditioned baseline insulin increase, and an increase in cortisol levels relative to baseline and cumulative number of neuroglycopenic sympt oms in the CS-placebo test session. The conditionability of glucose adminis tration also had to be examined; experiments using an arbitrary CS and gluc ose are extremely rare, even in animals. Glucose is the natural stimulus fo r endogenous insulin secretion, so studies on cephalic-phase insulin releas e (CPIR) will be reviewed in this paper. We implemented a placebo-controlle d three-group design (Experiment 2): Subjects received either CS-insulin, C S-glucose or CS-placebo pairings during the acquisition. Together, our resu lts demonstrate the conditionability mainly of insulin, but also of glucose effects in healthy humans. The clinical relevance and future research pers pectives are outlined with an emphasis on insulin in the brain and its role in learning and memory. (C) 2000 Elsevier Science B.V. All rights reserved .