An analysis of behavioural mechanisms involved in the acquisition of amphetamine anorectic tolerance

Abstract

Deprived rats given 2.5 mg/kg d-amphetamine before milk access developed anorectic tolerance. Rats given identical treatment after milk access did not exhibit tolerance in a subsequent test when the drug was given before milk access, nor did they subsequently acquire tolerance more rapidly than drug-naive animals. Manipulations of the amount of lab chow given to supplement milk intake did not affect the rate of development of tolerance, indicating that development of anorectic tolerance could not be explained in terms of increasing food deprivation or body weight loss as has often been suggested. The lack of tolerance in subjects drugged chronically after milk intake was shown not to be due to the development of a conditioned taste aversion in these animals. The possibility that tolerance was due to the acquisition of a classically conditioned compensatory response which attenuated drug effects was investigated. In one experiment the injection procedure was used as a potential conditioned stimulus. A series of placebo injections was given to tolerant rats in an attempt to extinguish any conditioned response, but this failed to attenuate tolerance. No compensatory hyperphagic response was seen after placebo injections. A further experiment was performed in which cues accompanying drug administration were made more salient by transferring animals to a distinct environment (noise, odour, light) after drug administration. Giving the drug subsequently in the home environment did not lead to the loss of tolerance predicted by the conditioning model, nor was there any evidence of hyperphagia in response to a placebo injection in the distinct environment. These results offer indirect support for a learning interpretation of amphetamine anorectic tolerance, but not one that involves classical conditioning of a compensatory response.