|Economics, Inhibition, and Self-Administration: Behavioral Pharmacology of Nicotine in Rats|
|Monday, May 26, 2014|
|3:00 PM–3:50 PM |
|W175a (McCormick Place Convention Center)|
|Area: BPH/EAB; Domain: Basic Research|
|Chair: Federico Sanabria (Arizona State University)|
Nicotine appears to enhance the value of reinforcing stimuli in the environment, and this effect may contribute to nicotines widespread abuse; tendencies toward impulsive behavior may also play a role in initiation and maintenance. While nicotine is the primary active ingredient in tobacco, cigarette additives, such as monoamine oxidase inhibitors, may increase sensitivity to nicotine. The present studies employed a variety of behavioral economic, response inhibition, and self-administration procedures in rodents that examined 1) the effect of nicotine on the essential value of food-paired conditioned reinforcers across fixed-ratio values in an observing response procedure, 2) the effect of acute and chronic nicotine on response inhibition and latency to initiate reinforcement trials, 3) the effects of pre-session injections of a monoamine oxidase inhibitor (tranylcypromine) on nicotine self-administration under conditions of escalating dose, and in a second experiment, under conditions of escalating fixed-ratio response requirement. In summary, nicotine 1) increased essential value, of food-paired conditioned reinforcers, and 2) increased impulsive responding, while 3) tranylcypromine increased sensitivity to nicotine dose.
|Keyword(s): behavioral economics, impulsivity, nicotine, self-administration|
Nicotine Increases the Essential Value of Food-Paired Conditioned Reinforcers
|RACHEL CASSIDY (Brown University), Jesse Dallery (University of Florida)|
Nicotine appears to enhance the value of reinforcing stimuli in the environment, and this effect may contribute to nicotines widespread abuse. We attempted to better quantify this by using the exponential demand equation, which gives an estimate of the essential value of a reinforcer. Six Long- Evans rats were exposed to an observing response procedure. In this procedure, two levers were concurrently available. Presses to one lever led to either food (according to a variable-interval 15s schedule) or extinction, which alternated according to a variable interval 60s schedule. Presses to a second, observing lever illuminated stimuli correlated with the schedule in effect on the food/extinction lever. The schedule-correlated stimuli served as conditioned reinforcers which maintained observing responding. The number of responses required on the observing lever increased across sessions (fixed-ratio schedule values: 1, 2, 3, 5, 7, 10). The number of conditioned reinforcers earned was plotted against FR value to generate a demand curve. Nicotine was then administered at a dose of 0.3 mg/kg. The exponential demand equation was then fit to the data. Compared to vehicle, nicotine increased the essential value of the conditioned reinforcers. The current analysis demonstrates that nicotine can increase the value of some conditioned reinforcers.
|Acute and Chronic Nicotine Decreases Response Inhibition Performance and Enhances the Reinforcing Efficacy of Sucrose|
|GABRIEL J. MAZUR (Arizona State University), Ann Nicole Hoffman (Arizona State University), Elizabeth Watterson (Arizona State Univerity), Lucas Richard Watterson (Arizona State University), Federico Sanabria (Arizona State University)|
|Abstract: Attention-Deficit Hyperactivity Disorder (ADHD) is associated with a substantially higher prevalence of smoking, which may be related to potential therapeutic effects of nicotine on ADHD symptoms. Whereas nicotine offers robust improvements on measures of attention, its effects on impulsivity are less clear. A series of studies examined the effects of nicotine on response inhibition in spontaneously hypertensive rats, an animal model of ADHD, compared to a normotensive control Wistar Kyoto using the Fixed Minimum Interval (FMI) schedule of reinforcement. On each FMI trial, the first lever press initiated an inter-response time (IRT); a head entry into a food receptacle terminated the IRT. IRTs longer than 6 s were intermittently reinforced with sucrose. Tests were conducted under a range of acute (0.1 – 0.6 mg/kg) and chronic (0.3 mg/kg) doses of subcutaneous nicotine. Pre-feeding probes evaluated effects of reinforcer devaluation. The temporal regulation model provided a close fit to the data, regardless of strain or treatment. No baseline difference in FMI performance was observed between strains. Nicotine reduced the duration of timed IRTs and the duration of latencies to the IRT-initiating lever press similarly for both strains. These results suggest that nicotine reduces response-inhibition and enhances the reinforcing efficacy of sucrose.|
Effects of Tranylcypromine, an Irreversible Monoamine Oxidase (MAO) Inhibitor, on Nicotine Self-Administration Behavior in Rats
|TRACY T. SMITH (University of Pittsburgh), Rachel L. Schassburger (University of Pittsburgh), Laura E. Rupprecht (University of Pittsburgh), Deanne M. Buffalari (University of Pittsburgh), Alan F. Sved (University of Pittsburgh), Eric C. Donny (University of Pittsburgh)|
Research has shown that low-dose nicotine self-administration behavior is increased by a pre-session injection of an irreversible MAO-inhibitor, tranylcypromine (TCP). The current studies further characterized the relationship between TCP and nicotine self-administration behavior across a range of nicotine doses and fixed ratios. In the first study, rats received pre-session injections of either TCP (1.0 mg/kg) or saline before daily intravenous nicotine self-administration sessions (FR2 schedule), and the nicotine dose was increased across sessions (0->1.875->3.75->7.5->15->30->60->90 ug/kg/infusion). The dose-response curve for the TCP group was shifted, indicating that TCP increases sensitivity to nicotine. In the second study, a behavioral economics procedure was employed in which rats responded for nicotine (15 or 60 ug/kg/infusion) and the FR was escalated across sessions (2->3->5->7->10->15->20->25->35->50->70->100->150). Rats receiving TCP and responding for 15 ug/kg/infusion nicotine had higher Q0 values, a free parameter generally affected by changes in dose or potency, but elasticity of demand was unchanged, consistent with the interpretation that TCP increases sensitivity to nicotine dose. Current studies are investigating the effect of lower TCP doses on nicotine self-administration. Preliminary data suggest that TCP doses producing substantially lower inhibition fail to produce an increase in nicotine self-administration.