Introduction

1. The Reinforcement Omission Effect as a Translational Model of Negative Urgency • Introduction • Impulsivity has been defined in various ways, and broadly “refers to factors that regulate the performance of inappropriate or maladaptive behaviors” (de Wit & Richards, 2004). • Urgency, or mood-based rash action, is a facet that has been developed to define one aspect of the multi-faceted construct of impulsivity (Whiteside & Lynam, 2001). • Urgency in humans is the tendency to engage in risky behavior due to extreme positive and negative affect (Cyders & Smith, 2008). • Negative urgency has been linked to increased alcohol use, binge/purging, pathological gambling, compulsive shopping, as well as stimulant drug use. • The current studies attempt to bridge the gap between questionnaire and behavioral models of impulsivity by developing a behavioral task of negative urgency that has good cross-species generality and that engenders individual differences in human performance which are consistent with construct measures on the UPPS personality questionnaire developed by Whiteside & Lynam (2001). • An operant analogue of the runway procedure from Amsel & Roussell (1952) was used, and a reinforcement omission effect (ROE) was predicted to occur following omission of reward in rat and human studies (Exp 1 and 2, respectively). • Method • Experiment 1 • Male Sprague-Dawley rats were initially trained with a CS (white cue light) – US (3 sucrose pellets) Pavlovian association. To determine if learning of the association occurred, a conditioned response (CR; a photo beam interruption) was used in the food receptacle (Figure 1). • Rats were then implanted with jugular catheters. Following recovery, rats were trained to self-administer d-amphetamine (AMPH; either 0.03 or 0.1 mg/kg/infusion). • Following acquisition, rats were given baseline training sessions in which a Pavlovian component was followed by an operant self-administration component until stable responding was achieved. Rats were then given test sessions with randomly intermixed omission trials in which the CS no longer led to sucrose pellets (see Figure 2). • Experiment 2 • Adults (age 18-36; n=18) completed the UPPS-R questionnaire (Whiteside & Lynam, 2001), in which level of negative urgency was measured (1 = not at all, 4 = a lot). • Subjects then completed an analogous procedure in which mouse clicks (FR-100) led to money following reward or reward omission (see Figure 3). Subjects were also required to complete visual analogue scale (VAS) questions randomly intermixed throughout the session (Figure 4). • Discussion • Both human subjects high in negative urgency and nonhuman subjects demonstrated increased responding following reward omission, thus adding to translational validity of this model. • At the 0.1 mg/kg/infusion dose, rats showed an ROE only in the first two test sessions. This is possibly due to anorectic effects with increased exposure to a high dose of AMPH, thus devaluing the US. • Human subjects rated high in negative urgency also reported increased VAS mood ratings of frustration, whereas those lower in urgency did not show this elevation from initial baseline levels. • Developing a negative urgency model in which a behavioral measure is predictive of urgency status is important because those who are high in negative urgency have been found to be at higher risk for drug use (e.g., alcohol). • Inconsistencies in definitions of impulsivity, as well as numerous behavioral tasks that do not directly map onto personality scales, have created difficulty in interpretation.Thus, the long-term goal of this project was to develop a valid translational model of a specific facet of impulsivity that may increase the risk for drug use as measured in personality scales with humans. • Future studies will include a rat saline control group, as well as a sucrose pellet group (in which responses during the operant component will lead to sucrose pellet delivery rather than a drug infusion) to illustrate the ROE with a nondrug reinforcer. Additional human subjects will be included in Experiment 2 as well. • Acknowledgements • Funding provided by NIH grants P50 DA1652, T32 DA007304, and the Center for Drug Abuse Research Petite Grant. Thanks to the Center for Drug Abuse Research Translation, Allen Mayberry, Emily Denehy, Julie Marusich, Chip Meyer, Kristin Alvers, Justin Yates, and Kate Fischer. Cassandra D. Gipson, Thomas H. Kelly, & Michael T. Bardo University of Kentucky • Figure 2. Schematic of a reward trial in Experiment • Omission trials consist of the cue light leading to • no sucrose pellets in the initial Pavlovian component. Figure 1. Conditioned responding during initial Pavlovian pretraining in Experiment 1. Figure 4. (a) VAS questions during human behavioral task, consisting of a set of 8 questions (do you feel stressed, irritated, energetic, frustrated, content, alert, anxious, or active). (b) and (c) VAS ratings from 3 human subjects high in urgency in Experiment 2. Figure 3. Schematic of a reward trial in Experiment 2. Omission trials consist of the cue light leading to no sucrose pellets in the initial Pavlovian component. a. Figure 5. Response rate (lever presses/trial) on test sessions during (a) 0.03 mg/kg/infusion and (b) 0.1 mg/kg/infusion AMPH self-administration in Experiment 1 Figure 6. Correlations of behavioral measure (ratio of mouse clicks/sec/trial) and personality questionnaire ratings of (a) negative urgency, (b) sensation seeking, (c) premeditation (lack of), and (d) perseverance (lack of) in Experiment 2. R square = 0.6470, F(1,16) = 29.32, p < .0001 R square = 0.016, F(1,16) = 0.2599, p = 0.6172 R square = 0.1274, F(1,16) = 2.335, p = 0.146 R square = 0.1679, F(1,16) = 3.229, p = 0.0912