Figure 4. Exposure to forced swim stress produces a nor-BNI-sensitive potentiation of cocaine-conditioned place preference.A, Schematic of training paradigm. The CPP protocol was as described in Materials and Methods. Preference testing allowed mice to move freely for 30 min in the morning to measure preconditioning and subsequent responses for either of two conditioning chambers, as described in Materials and Methods (represented here by triangles). After assessment of preconditioning preference, mice were exposed to repeated forced swim stress over the next 24 hr, as detailed in Materials and Methods (diamonds), or allowed to remain in home cages without swimming. Within 10 min after forced swim testing on day 2, mice were administered cocaine (15 mg/kg, s.c.) and confined to the drug-paired box for a 30 min conditioning session (squares). Four hours later, mice were administered vehicle and confined to the vehicle-paired box for a 30 min conditioning session (circles). Cocaine and saline conditioning was repeated the next day, separated again by 4 hr (represented by joined square and circle, day 3). On day 4, the final preference test was performed blind to determine the effect of treatment and conditioning on place preference. B, Preference test data demonstrating a nor-BNI-sensitive, FST-induced potentiation of cocaine CPP. Preferences are given as the difference between time spent in the drug-paired chamber and time in the saline-paired chamber during the 30 min trial. A positive value represents time spent in the drug-paired chamber. Mice were divided into three groups. The first group was unstressed, remaining in home cages and not exposed to swim stress before 2 d of cocaine and saline conditioning, as described in Materials and Methods (black bar). The second group was administered vehicle and exposed to the forced swim stressor before 2 d of cocaine and saline conditioning (light gray bar). The third group was administered nor-BNI, exposed to the forced swim stressor as described above, and then conditioned over 2 d with cocaine and saline (dark gray bar). After conditioning, all three groups demonstrated an increase in time spent in the cocaine-paired chamber that was significantly greater than the time spent in that chamber before conditioning, an example of conditioned place preference. Control unstressed mice and nor-BNI-treated, FST-exposed mice demonstrated an equivalent degree of cocaine CPP. In contrast, vehicle-treated mice exposed to FST demonstrated a significant potentiation over the unstressed animals responses. Note that mice did not demonstrate significant differences in body temperature from unstressed mice immediately after forced swimming, immediately before place conditioning, or 30 min after cocaine administration. *Significant difference in cocaine CPP compared with CPP for both unstressed and nor-BNI-treated mice; p<0.05, as determined by ANOVA followed by Student's t test. Bars represent n = 11–16 mice.