Exposure to adverse events is a risk factor for substance use disorder. We modeled this in an inbred strain of mice by exposing adult males to a predator odor (a synthetic fox pheromone, TMT) and then assessing 1. Cocaine-induced locomotion, and 2. Conditioned place preference (CPP) of cocaine. TMT was an effective stressor as indicated by freezing behavior, an absence of movement that is an instinctive fear response in mice. Interestingly, in a 1-hour baseline locomotor test, TMT-exposed (TMT+) mice were more active than non-exposed (TMT-) mice. In addition, following a cocaine (10 mg/kg) injection (i.p.) TMT+ mice showed a cocaine-induced increase in activity, whereas TMT- mice did not. Finally, mice were conditioned to associate one side of a 3-chambered arena with cocaine (10 mg/kg) and were then tested in a 30-minute session of free exploration (15 minutes of cue-prime, 15 minutes of drug-prime). One week later, an identical 30 min session of free exploration was conducted. The time spent inside the drug-associated context was considered an indication of the rewarding properties of cocaine
