Characterization of the associative nature of sensitization to amphetamine-induced circling behavior and of the environment dependent placebo-like response.

Amphetamine-induced circling behavior increases over the course of repeated administration of the drug; likewise, after repeated administration of amphetamine, an injection of saline prior to placement of the rat in the test apparatus previously associated with the pharmacologic effects of amphetamine will increase circling behavior. Experiments were designed to determine if either of these effects would respond to manipulation of the temporal contiguity between the test environment and the peak effects of amphetamine. The placebo-like response, in accordance with a Pavlovian conditioned response, was reduced by prior non-reinforced exposure to the test environment and subject to extinction. In contrast, the increase in the amphetamine-induced response was entirely dependent on the test environment but not affected by latent inhibition or extinction. These and previous findings indicate that the development and expression of the placebo-like response is the result of a Pavlovian associative process. Although amphetamine sensitization is environment dependent, it does not resemble a conditioned response in other respects.