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.

Excitatory conditioning to the interoceptive nicotine stimulus blocks subsequent conditioning to an exteroceptive light stimulus

“…The results of the current experiment add to this sparse literature by demonstrating that nicotine can also block a visual stimulus in a Pavlovian drug discriminated goal-tracking task. The current findings also add blocking to the list, along with overshadowing [15], of cue competition phenomenon involving nicotine as an interoceptive stimulus element.…”

“…The amount of behavioral control exerted by each stimulus element is presumably based on the salience (perceptibility) of that element relative to the other element [12-14]. We have previously shown that the IV nicotine stimulus competes with an exteroceptive light stimulus when trained as a compound CS [15]. In those experiments, cue-lights near the dipper receptacle were presented during the 30-sec interval between nicotine infusion and access to sucrose.…”

“…The present experiment sought to fill this gap by assessing whether previous excitatory conditioning with the nicotine CS would block subsequent conditioning to an exteroceptive light CS. We expect the nicotine CS to block conditioning to the light CS given our recent demonstration of overshadowing using this light plus nicotine compound stimulus [15]. …”

“…Catheter patency was assessed with a 0.05 ml IV infusion of xylazine (20 mg/ml) at pre-established points in each study [cf. 15; 17]. Only rats with patent catheters were included in analyses.…”

High-dose adolescent nicotine exposure permits spontaneous nicotine self-administration in adult male rats

“…Precision infusion pumps automatically adjusted infusion duration for each rat's weight on a given day to keep dosing consistent. Nicotine pH was adjusted to 7.0-7.2 (Charntikov et al, 2020;Murray et al, 2011;Palmatier et al, 2006;Schassburger et al, 2015;Swalve et al, 2016) using NaOH and was prepared fresh weekly.…”