Can the discriminative stimulus effects of nicotine function concurrently as modulatory opponents in operant and pavlovian occasion setting paradigms in rats?

Abstract

Nicotine promotes interoceptive changes in the nervous system. Such interoceptive stimuli play important roles in modulating addictive behavior. Operant and Pavlovian stimulus control modulate responsiveness to environmental stimuli related to drug-seeking and self-administration. Nicotine functions as a discriminative stimulus in modulating operant behavior as well as Pavlovian feature stimuli in modulating the conditional responding (CR) to exteroceptive CS→US contingencies. Elucidation of the interaction of these interoceptive stimulus control functions is vital for a comprehensive understanding of nicotine use/abuse, which might lead to better behavioral treatment strategies. This experiment evaluated the interaction among Pavlovian feature positive (FP) and feature negative (FN) effects of nicotine on concurrently occurring operant S^D and S^Δ effects. Sixteen rats were trained in a Pavlovian and operant bidirectional contingency paradigm, using nicotine (0.3 mg/kg) and non-drug (saline) states as interoceptive cues for operant discriminative stimulus conditions (S^D and S^Δ) as well as Pavlovian FP and FN for a light-CS, either leading to a shared food pellet outcome or non-outcome. Nicotine and saline sessions were intermixed. For one group of rats (n = 8), nicotine served as an S^D for lever pressing (variable interval 60 s) and simultaneously functioned as an FN for CS-light→noUS relation on the same sessions. On intermixed sessions, saline served as the S^Δ for lever pressing (non-reinforced) and FP, during which the 8-sec light preceded delivery of the food pellet (variable time ITI = 60 s). For the other group (n = 8) nicotine served as the S^Δ (lever pressing non-reinforced) and FP for the CS, with saline serving in the reverse roles. Consecutive brief non-reinforcement tests revealed that: A) rates of lever pressing were significantly greater in S^D than S^Δ with nicotine and saline suggesting strong operant discriminative stimulus control; B) FP responding to the light CS with nicotine and saline was evident; and C) FN suppression of the CR with nicotine was not evident but weak under saline. These data suggest that nicotine can function as an interoceptive context that hierarchically can enter into concurrently opposing modulatory relations in Pavlovian and operant drug discrimination procedures.

Keywords: Bidirectional conditioning; Drug discrimination; Feature negative; Feature positive; Interoception; Nicotine; Occasion setting; Rats; S(D); S(Δ).