Factors regulating drug cue sensitivity: the effect of frustrative non-reward in fentanyl-saline discrimination.

In this study, rats were trained to discriminate 0.04 mg/kg of fentanyl from saline in two-lever food-reinforced procedure. The study examined the effects of a manipulation of reinforcement (i.e. frustrative non-reward; FNR) on several characteristics of fentanyl-saline discrimination. It was found that asymmetrical FNR in either saline or drug sessions retarded the acquisition of the discrimination and codetermined response bias; symmetrical FNR in both types of sessions had no effect. Asymmetrical FNR in saline sessions steepened the slope of the generalization of fentanyl, but also of morphine and sufentanil; asymmetrical FNR in drug sessions flattened the gradient's slope. Symmetrical FNR had effects on slope which were similar to those of asymmetrical FNR in saline sessions. Both symmetrical and asymmetrical FNR also appeared to affect the ED50-value of different agonists, and the ED50-value of naloxone in antagonizing 0.04 mg/kg of fentanyl. It thus appears that reinforcement plays a major role in the acquisition of fentanyl-saline discrimination and in the quantitative characteristics of the stimulus generalization gradient of fentanyl and other agonists. It is also suggested that the training drug itself may interact with the effects of FNR on its own gradient.