An established preference for a conditioned stimulus associated with either sucrose or copulation in male rats subsequently shifts to a preference for a conditioned stimulus paired with cocaine self-administration

It is often assumed that a characteristic of drug addiction is a loss of interest in natural rewards concomitant with a heightened interest in drug rewards. To test this idea, we gave male rats a choice between a conditioned stimulus associated with a natural reward (sex or sucrose) and a conditioned stimulus associated with cocaine. In the first experiment, male rats were given five trials in which an odor (either lemon or almond) was associated with copulation to ejaculation with a sexually receptive female. Males were then given a choice between the odor-sex testing box and a neutral box (Day 1:15- min test). Rats showing a clear preference for the odor (n=10) then learned to self-administer cocaine in the presence of the other odor. After 3 cocaine sessions given on 3 consecutive days, they were given a choice test between the odor-sex and the odor-cocaine boxes (Day 10). The following day, there was an additional odor-sex pairing after which there were three additional days of odor-cocaine self-administration. Odor choice tests were given subsequently on Days 17, 24 and 38 without additional training. The odor preference of all rats did not shift immediately,but by day 38, 70% of the males chose the cocaine-paired odor. In Experiment 2, parallel results were observed in males (n=12) first trained to associate an odor with lever-pressing for sucrose pellets and then tested for the odor-sucrose box preference on Day 1. After training to self- administer cocaine in the presence of the second odor, rats developed a quick and consistent preference for the odor associated with cocaine. These results provide preliminary evidence that cocaine induces a preference shift in rats away from stimuli associated with natural rewards to stimuli paired with repeated drug self- administration. These experiments also demonstrate the effectiveness of the method for the further study of the phenomenon.