Amphetamine-induced conditioned activity does not result from a failure of rats to habituate to novelty.

Psychostimulant-induced conditioned activity is characterized by the presence of a hyperactivity in drug-free rats exposed to an environment previously paired with the effects of a psychostimulant. According to the habituation hypothesis, conditioned activity arises not through a Pavlovian conditioning process but rather because rats under the effects of the psychostimulant would be unable to habituate normally to the environment paired with these effects. This hypothesis predicts that conditioned activity should not develop in a previously habituated environment. This prediction was tested using a within-subject design. In this design, conditioned activity is evidenced when a group of rats, following a vehicle injection, was more active in a previously amphetamine-paired environment than in a previously vehicle-paired environment. The drug-environment pairing involved administering rats with d-amphetamine (1.25 mg/kg; SC) immediately prior to their placement in one of two distinctive environments. On alternate days, the rats received the vehicle and were placed in the other environment. With this design, it was found that: a) conditioned activity developed in a previously habituated environment; b) its magnitude was independent of the number of amphetamine-environment pairings (two, four or eight pairings); c) this development of conditioned activity did not result from a forgetting of the habituated environment due to a state-dependent retention of the habituation. Taken together, these results do not support the habituation hypothesis of psychostimulant-induced conditioned activity.