In Experiment 1, a dose-response study ofplace conditioning with amphetamine was conducted. Male Sprague-Dawley rats receiving 0.0, 0.05, 0.1, 0.5, 2.0, 5.0, 7.5, or 10.0 mglkg of d-amphetamine underwent 10 4-day cycles ofplace conditioning. On alternate days, each rat was injected with its designated dose of amphetamine while confined to its originally nonpreferred end of a three-compartment, straight alley box. On intervening days, each rat was injected with saline while confined to its originally preferred compartment. Following each 4-day cycle, a choice test was administered in which each rat was allowed 20 min of access to the entire alley box. Doses of amphetamine (~0.5 mglkg) induced a significant avoidance of the compartment in which amphetamine had been administered. In Experiment 2, animals received 0.0, 0.5, 2.0, or 5.0 mglkg of amphetamine and underwent place conditioning procedures identical to those for the animals in Experiment 1. Unlike in Experiment 1, the animals were given a single choice test following 10 4-day place conditioning cycles. All groups that received amphetamine exhibited a conditioned place avoidance. In Experiment 3, the effect ofvarious es-ucs intervals on place conditioning with 2.0 mglkg of amphetamine was examined. Animals that received amphetamine immediately following their removal from the chamber exhibited a conditioned place avoidance.

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Tolerance and cross-tolerance among several anorectic drugs were investigated in four separate tests. The same animals served as subjects in all four tests. In the first test, animals given milk shortly after injection of 3 mg/kg amphetamine (Cont group) developed tolerance to amphetamine anorexia, but animals given milk when amphetamine's anorectic effects had worn off (Noncon group) did not develop tolerance in spite of equal drug exposure. In the second test, Cont animals were tolerant to 2 mg/kg apomorphine, a drug with a neurochemical action related to amphetamine. No tolerance to 2 mg/kg apomorphine was shown by the Noncon animals. Next, it was found that both Cont and Noncon groups were tolerant to a smaller dose of 1.25 mg/kg apomorphine. The final test replicated part of the first test; that is, the Cont group was tolerant to amphetamine, but the Noncon group was not. In addition, animals in neither group were tolerant to anorexia produced by 5 mg/kg fenfluramine, a drug whose action is neurochemically different from amphetamine and apomorphine. From these experiments it appears that both learning and specific neurochemical mechanisms are involved in the development of tolerance to anorectic drugs.

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