Delay discounting is rapidly emerging as an important topic in substance abuse research as it becomes clear that drug abusers value delayed rewards less than non-abusers. It is not clear whether this change in discounting is a cause or a consequence of drug taking, although there is evidence to support both possibilities. An in-depth understanding of the neural circuitry underlying delay discounting and how these substrates are affected by drugs of abuse could facilitate a better understanding of vulnerability as well as promote new advances in the treatment of substance abuse. Brain imaging technology is a powerful tool for investigating functional neural pathways. Brain imaging studies on delay discounting in humans provide valuable information, yet practical and ethical limitations necessitate complimentary studies with nonhumans. Unfortunately, currently available rodent models of delay discounting are incompatible with brain imaging in behaving subjects. Studies in this application develop a delay discounting procedure in nonhuman primates that will be compatible with brain imaging. The proposal consists of two parallel, independent specific aims (delay discounting [1] and imaging [2]) that will merge in a future RO1 application. Studies in Aim 1 develop a delay discounting procedure for rhesus monkeys, compatible with functional magnetic resonance imaging (fMRI). Separate groups of monkeys (n=4 per group) will be trained with either oral (drinking) delivery of a preferred liquid (e.g., juice) or i.v. delivery of drug (remifentanil) as the reinforcer. The delay discounting procedure with monkeys is nearly identical to procedures that are used to study delay discounting in humans and rodents.
Aim 2 develops procedures and tools for acquisition, processing, and interpretation of fMRI studies, in this application in anesthetized monkeys and eventually in awake, behaving monkeys. Collectively, these developmental studies (R21) provide the foundation for a future RO1 application investigating the neural substrates underlying delay discounting and how these substrates are affected by drugs of abuse. Impulsivity is thought to be both a predisposing factor and a consequence of drug abuse; this grant develops a nonhuman primate model of delay discounting for examining the behavioral and neural consequences and causes of impulsivity. Such a model is not currently available but is essential for understanding how impulsivity and drugs interact and, therefore, how treatments for drug abuse can be tailored based on the behavioral output (e.g., impulsivity) of individuals. ? ? ?
| Maguire, David R; Li, Jun-Xu; France, Charles P (2012) Impulsivity and drugs of abuse: a juice-reinforced operant procedure for determining within-session delay discounting functions in rhesus monkeys. J Pharmacol Toxicol Methods 66:264-9 |
