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 CSUS 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 SD and SD 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 (SD and S∆) 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 SD for lever pressing (variable interval 60 sec) and simultaneously functioned as an FN for CS-lightnoUS relation on the same sessions. On intermixed sessions, saline served as the SDfor lever pressing (non-reinforced) and FP, during which the 8-sec light preceded delivery of the food pellet (variable time ITI = 60 sec). For the other group (n=8) nicotine served as the SD (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 than SD 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.

Impact of the Aversive Effects of Drugs on Their Use and Abuse

“…Characteristics of maintained drug self-administration indicate that drug or drug-associated stimuli encountered by an animal in a drug-free state will initiate drug intake, but when the drug level reaches above a satiety threshold, i.e., the minimal drug level at which self-administration is maintained, animals temporarily suspend drug seeking [ 15 , 280 ]. Consistent with this position, the presence or absence of a drug in the biological system has been demonstrated to serve discriminative functions that signal the availability of certain reinforcers, e.g., food and water [ 285 – 288 ]. Not only can drugs serve as discriminative stimuli in general but also the discriminative control of the training drug can also be generalized to drugs with comparable mechanisms of action [ 289 – 292 ].…”

Sex differences in extinction and reinstatement of nicotine discrimination in rats: The effects of reinforcer devaluation.

“…Historically, the operant drug discrimination paradigm with rodents has proven to be valuable preclinically for evaluating the interoceptive stimulus effects of psychoactive drugs of use and abuse (Overton, 1982), including nicotine (Shoaib & Perkins, 2020); it has also been used theoretically to investigate associative phenomena embedded within the interoceptive stimulus functions of nicotine (e.g., Troisi & Michaud, 2019). Interestingly, there is a paucity of animal research examining sex differences in the stimulus functions of nicotine and other drugs (Bevins & Charntikov, 2015).…”