Interoceptive Pavlovian conditioning with nicotine as the conditional stimulus varies as a function of the number of conditioning trials and unpaired sucrose deliveries

Abstract

In rats, the pharmacological (interoceptive) effects of nicotine can serve as a signal (conditional stimulus) in a Pavlovian (classical) conditioning task. In this task, nicotine administration (0.4 mg base/kg, subcutaneous) is typically paired with intermittent access to a liquid sucrose unconditional stimulus; sucrose is withheld on saline sessions. An increase in sucrose receptacle entries (goal tracking) on nicotine sessions indicates conditioning. Given our limited understanding of the functional relationships controlling conditioned responding to a nicotine conditional stimulus, the present research examined nicotine's sensitivity to several manipulations shown to affect the conditioned responding in more widely studied Pavlovian conditioning tasks that use exteroceptive conditional stimuli: number of nicotine conditional stimulus-sucrose unconditional stimulus pairings per session (0, 3, 9, 18, or 36) and the impact of sucrose deliveries in saline sessions. Differential goal tracking developed in fewer sessions and asymptotic conditioned responding magnitude was greater with more nicotine-sucrose pairings. Further, goal tracking was more resistant to extinction (unconditional stimulus withheld) with more conditional-unconditional stimulus pairings during the acquisition phase. The discrimination was not acquired when sucrose presentations (9 or 18) also occurred during saline sessions. Furthermore, expression of the discrimination was disrupted when sucrose was presented in saline sessions; this disruption resulted from goal tracking in saline sessions. These results are consistent with the notion that nicotine-evoked goal tracking results from interoceptive conditioning processes.

Nicotine does not produce state-dependent effects on learning in a Pavlovian appetitive goal tracking task with rats

“…Experiment 1 of the present report extends this research by showing that a fading procedure is not required for a 0.2 mg/kg dose of nicotine to function as interoceptive CS. Although one must be cautious when comparing across studies, there does not appear to be any obvious difference in acquisition of the discrimination between the present study and previous research using 0.4 mg/kg nicotine [36]. Further research, however, is needed to directly assess whether this dose of nicotine affects acquisition and/or maintenance of conditioned responding.…”

“…Previous research from our laboratory has shown that 0.4 mg/kg of nicotine paired reliably with sucrose acquires the ability to control a goal-tracking CR [4,36]. Further, a 0.2 mg/kg dose of nicotine also served as an interoceptive CS using a fading procedure [7].…”

“…Recently, we have published several examples of a Pavlovian drug discrimination task in rats using the pharmacological effects of nicotine (0.4 mg base/kg) as the interoceptive CS and 4-sec access to liquid sucrose as the US [4,7,36]. In brief, on nicotine sessions rats have intermittent access to sucrose, whereas on saline sessions no sucrose occurs.…”

Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus

“…Using head entries into the sucrose receptacle before the fi rst sucrose delivery as a measure of conditioning (i.e., goal tracking; Boakes, 1977 andFarwell andAyres, 1979), nicotine readily served as a conditional stimulus as evidenced by increased dipper entries on nicotine compared to saline sessions. Importantly, when a group of rats had access to sucrose on both nicotine and saline sessions, differential conditioned responding did not develop (Wilkinson et al, 2006b).…”

“…Nicotine can also cue when a discrete light conditional stimulus will not be followed by sucrose, thereby serving as a negative drug feature (Bevins et al, 2006). Nicotine has also recently been shown to serve as an interoceptive contextual conditional stimulus for access to sucrose in rats (Besheer et al, 2004 andWilkinson et al, 2006b). Briefl y, in that research, a subcutaneous (s.c.) injection of 0.4 mg base/ kg nicotine or saline was given 5 min before placement in a conditioning chamber.…”