Impulsivity, an increased tendency to act without thought or deliberation, is common in psychiatric disorders and often is observed in drug abusers. Although impulsivity might be a predisposing trait that contributes to the development of substance abuse, it might also be a result of drug use, thereby promoting ongoing abuse and possibly relapse. Studies have examined how acute administration of drugs affects impulsivity;however, most drug abuse involves repeated drug administration and often the development of physical dependence, yet few studies have examined how impulsivity is affected by chronic drug administration and its discontinuation. Impulsivity is multidimensional and several procedures have been developed for studying different but equally important dimensions of impulsivity;in one procedure, delay discounting, subjects choose between a smaller reinforcer that is delivered without delay and a larger reinforcer that is delivered after a delay. Increased responding for the smaller, immediately available reinforcer is thought to reflect greater impulsivity. Studies in this application examine effects of acute and chronic opioid treatment, and its discontinuation, on delay discounting in animals because in humans delay discounting is sensitive to opioid treatment and its discontinuation. Data from humans suggest that impulsivity contributes to drug abuse and that drug abuse increases impulsivity;delay discounting might also vary across different reinforcers (e.g., money versus drug). Proposed studies build on preliminary data showing that delay discounting is affected by daily administration of very small doses of morphine, suggesting that abuse of even small doses of drugs (e.g., prescription opioids) could significantly increase impulsivity. These studies examine how acute and chronic treatment with a prototypic 5 opioid receptor agonist (morphine), as well as discontinuation of treatment, impact delay discounting in adult male rhesus monkeys. Studies under AIM 1 build on preliminary studies and compare acute drug effects on delay discounting in monkeys responding for a non-drug reinforcer to effects in monkeys responding for a drug reinforcer;these studies test whether delay discounting is differentially altered when responding is maintained by different reinforcers and also test the pharmacologic selectively of these drug effects. Using the same monkeys, AIM 2 evaluates how chronic treatment with morphine and its discontinuation alter delay discounting under the non-drug and drug reinforced procedures;these studies examine the effects of daily treatment on delay discounting, whether tolerance develops to those effects, how discontinuation modifies delay discounting, and how the time course of changes in this measure of impulsivity correlates with indices of withdrawal. These studies examine the unexplored possibility that abuse of even small doses of opioids increases impulsivity that can be enduring;increased impulsivity might contribute to ongoing drug abuse, relapse, and other high risk behavior long after drug withdrawal is no longer evident.
Impulsivity puts you at risk for drug abuse, but might also be caused by it, although little is known about how drug use, especially chronic drug use, impacts impulsivity. This grant examines the effects of chronic drug administration and its discontinuation (withdrawal) on delay discounting to determine how common drugs of abuse affect impulsivity.
|Minervini, Vanessa; France, Charles P (2018) Effects of morphine/CP55940 mixtures on an impulsive choice task in rhesus monkeys. Behav Pharmacol 29:60-70|
|Maguire, David R; Gerak, Lisa R; France, Charles P (2016) Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Behav Pharmacol 27:155-64|
|Maguire, David R; Gerak, Lisa R; France, Charles P (2016) Delay discounting of the ?-opioid receptor agonist remifentanil in rhesus monkeys. Behav Pharmacol 27:148-54|
|Lamb, R J; Maguire, David R; Ginsburg, Brett C et al. (2016) Determinants of choice, and vulnerability and recovery in addiction. Behav Processes 127:35-42|
|Koek, Wouter; Gerak, Lisa R; France, Charles P (2015) Effects of amphetamine, morphine, and CP 55,?940 on Go/No-Go task performance in rhesus monkeys. Behav Pharmacol 26:481-4|
|Maguire, David R; Gerak, Lisa R; France, Charles P (2013) Delay discounting of food and remifentanil in rhesus monkeys. Psychopharmacology (Berl) 229:323-30|
|Maguire, David R; Gerak, Lisa R; France, Charles P (2013) Effect of delay on self-administration of remifentanil under a drug versus drug choice procedure in rhesus monkeys. J Pharmacol Exp Ther 347:557-63|
|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|