Nicotine competes with a visual stimulus for control of conditioned responding

Abstract

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.

Figure 1

Acquisition and maintenance of compound stimulus training. Mean conditioned responding [±1 standard error of the mean (SEM)] for each training session in all groups is shown (a). Conditioned responding in acquisition and maintenance phases of compound training with results of the element test sessions (+1 SEM) are shown for the individual training groups (b–f ).The order of element test presentation is for display purposes only; they were conducted in a counterbalanced manner (see Procedures). Significant results are described in the text

Figure 2

Tests 1 and 2 (a and b, respectively) of the proportion of total elevation scores (+1 SEM) for responding on the nicotine and light test trials for each of the five groups are shown. * denotes significant difference between proportion of responding on the nicotine and light elements within the group. + denotes a significantly higher proportion of nicotine-evoked responding compared with the 0 mg/kg group. # denotes a significantly lower proportion of light-evoked responding compared with the 0 mg/kg group

Figure 3

Acquisition and maintenance of stimulus training. Mean elevation scores (±1 standard error of the mean) of acquisition and element tests for the four training groups in Experiment 4 (a, b, c and d display the N−/L+, N+/L−, NL+, and NL− groups, respectively) are shown. The order of element test presentation is for display purposes only; they were conducted in a counterbalanced manner (see Procedures). Significant effects are described in the text

Figure 4

Tests 1 and 2 (a and b, respectively) of elevation scores (+1 standard error of the mean) for the nicotine and light test trials for each of the four groups are shown. * denotes significant difference between responding on the nicotine and light elements within the group. + denotes significantly lower nicotine-evoked responding compared with the N+/L− group. # denotes significantly lower light-evoked responding compared with the N−/L+ group