Cocaine-conditioned activity persists for a longer time than cocaine-sensitized activity in mice: implications for the theories using Pavlovian excitatory conditioning to explain the context-specificity of sensitization.

The present study was aimed at testing the prediction of the Pavlovian excitatory conditioning explanation of context-specific sensitization that the sensitized effect (SE) should persist as long as the post-sensitization conditioned activity (CR). C57BL/6J mice were tested for the expression of cocaine-induced conditioned and sensitized locomotion on several intervals after the establishment of a sensitization in an unchanging context. A group of mice received 10 once-daily injections of 10 mg/kg cocaine (s.c.) in a short time prior to being tested in activity-meters for 60 min sessions (cocaine-pretreated group), mice from a control group receiving saline in the same manner (saline-pretreated group). On the test sessions, taking place 1, 8 and 28 days after cocaine pretreatment, half of the animals of each pretreatment group (n=8) received a challenge test with saline and the other half with 10 mg/kg cocaine in the pretreatment context room (for CR and SE tests, respectively). The CR was significantly expressed on the three successive saline-challenge tests, albeit the activity levels were markedly decreased on the 28-day retention test. In contrast, the SE was significantly expressed only during the first half of the 1-day test session and the first 10 min of the 8-day test session, no SE effect being expressed on the 28-day retention test. The results, suggesting a functional uncoupling of the CR from the SE, disprove the theories of context-specificity of sensitization based completely or partially on Pavlovian excitatory conditioning mechanisms.