Conditioned flavor aversions: a toxicity test of the anticholinesterase agent, physostigmine.

The viability of the conditioned flavor aversion test as a behavioral index of the toxicity of physostigmine, an anticholinesterase agent, was evaluated in a series of three experiments. Experiments 1 and 2 used the flavor aversion paradigm and Experiment 3 used a more traditional behavioral testing paradigm in which the effect of physostigmine on a specified set of behaviors was measured. In the flavor aversion paradigm, the rats were allowed to consume 0.5% saccharin solution before being injected with one of various doses of physostigmine (0.025--0.50 mg/kg) or saline. They were subsequently tested for a learned flavor aversion by means of a one-bottle test in Experiment 1 and a two-bottle test in Experiment 2. In the behavioral testing paradigm used in Experiment 3, each rat was injected with one of various doses of physostigmine within the range of those used in the prior experiments, and thirty minutes later was placed in a chamber for observation for 15 minutes. The procedures of Experiment 3 were much more time consuming than those of Experiments 1 and 2. By the two-bottle aversion test of Experiment 2, a dose as low as 0.05 mg/kg of physostigmine produced a reliable flavor aversion which persisted for three extinction test trials. On the other hand, robust and reliable behavioral differences of decreased rearing and consumption of water in Experiment 3 were only evident in rats given 0.25 mg/kg of physostigmine. We conclude that the flavor aversion test is a simple and sensitive behavioral measure of toxicity.