Nicotine competes with a visual stimulus for control of conditioned responding

Environmental stimuli that co-occur with tobacco use come to evoke drug-related conditioned responses (CRs) that appear involved in continued use of nicotine-containing products. In rats, nicotine can serve as a conditional stimulus (CS) for non-drug unconditioned stimuli (USs), prompting the question of whether the nicotine CS can compete with, or overshadow, a non-drug environmental stimulus for control of a CR. In Experiment 1, male Sprague-Dawley rats were assigned to a group [0, 0.01, 0.03, 0.045, or 0.06 mg nicotine (base)/kg/infusion]. During each session, there were 10 intravenous infusions followed by a 30-second houselight to form a compound CS. At light offset there was 4-second access to sucrose. For Experiment 2, groups were nicotine (0.03 mg/kg/infusion) + light compound paired, nicotine + light compound unpaired, nicotine paired and light unpaired, and nicotine unpaired and light paired. Paired stimuli were presented with sucrose similar to Experiment 1. Unpaired stimuli were temporally separated from sucrose. Following acquisition, tests of nicotine and light alone were conducted by intermixing non-reinforced trails into training sessions. Nicotine dose-dependently overshadowed the light CS as shown by reduced light control of conditioned responding with higher doses. The nicotine, light, and nicotine + light compound had to be paired with sucrose to evoke a CR. These results demonstrate nicotine overshadows an exteroceptive visual stimulus. Because exteroceptive stimuli are often the focus of cue-exposure therapy, such competition may help begin to explain the marginal effectiveness of these therapies.