Loss of tolerance to amphetamine-induced hypophagia in rats: Homeostatic readjustment vs. instrumental learning

According to the homeostatic model, the loss of tolerance to amphetamine-in duced hypophagia requires a period of unrestricted feeding in the drug-free state, which transforms the compensatory response mediating tolerance ("hy perhunger") into a functional disturbance to homeostasis. In the absence of such a disturbance, tolerance should be retained. To test this prediction, rats tolerant to amphetamine's hypophagic effect were given a 4-week toler ance retention period during which milk intakes were restricted and depriva tion levels held relatively constant. During this period the rats were assi gned to one of the following drug treatment conditions: 1) saline injection s both before and after daily milk tests (saline group); 2) saline injectio ns before, and amphetamine injections after, daily milk tests (after group) ; 3) no injections and no milk tests (no-treatment group); or 4) amphetamin e injections before, and saline injections after, milk tests (before group) . Despite the restricted feeding regimen, both the saline and after groups Lost tolerance. These results do not support the homeostatic model, but are consistent with the instrumental learning model, which views drinking milk in the undrugged state as analogous to receiving noncontingent reinforceme nt. (C) 1999 Elsevier Science Inc.