Self-administered cocaine causes long-lasting increases in impulsive choice in a delay discounting task.

Abstract

Cocaine use is associated with high levels of impulsive choice (preference for immediate over delayed rewards), but it is not clear whether cocaine use causes elevated impulsive choice, or whether elevated impulsive choice is solely a predisposing factor for cocaine use. This study examined the effects of prior cocaine self-administration on rats performing a delay discounting task commonly used to measure impulsive choice. Male Long-Evans rats were implanted with intravenous catheters, and following recovery, were trained to self-administer 30 mg/kg/day cocaine HCl (approx. 0.5 mg/kg/ infusion) for 14 consecutive days (a control group received yoked intravenous saline infusions). Following three weeks of withdrawal, all rats were food-restricted and began training on the delay discounting task in standard operant chambers. On each trial, rats were given a choice between two levers. A press on one lever delivered a small food reward immediately, and a press on the other delivered a large food reward after a variable delay period. Rats that self-administered cocaine displayed greater impulsive choice (enhanced preference for the small immediate over the large delayed reward, as reflected by shorter indifference points) compared to controls, but were no different from controls on a "probabilistic discounting" task in which they chose between small certain and large uncertain rewards. These data suggest that self-administered cocaine can cause lasting elevations in impulsive choice, and that the high levels of impulsive choice observed in human cocaine users may be due in part to long-term effects of cocaine on brain function.

Adolescent Risk Taking, Cocaine Self-Administration, and Striatal Dopamine Signaling

“…The finding of increased risk taking following cocaine SA is consistent with a large body of literature showing that cocaine exposure causes lasting alterations in other aspects of cognition and motivated behavior (Dandy and Gatch, 2009;Mendez et al, 2008;Mendez et al, 2010;Saddoris et al, 2011;Schoenbaum and Setlow, 2005;Simon et al, 2007). It is also consistent with findings of increased impulsivity and risk taking in cocaine users (Bechara et al, 2001;Bolla et al, 2003;Coffey et al, 2003).…”

“…Animal models have provided considerable insight into the nature and direction of relationships between some maladaptive behaviors and drug use. For example, high levels of impulsive choice predict both acquisition and escalation of cocaine self-administration, which in turn can cause increases in impulsive choice (Anker et al, 2009;Mendez et al, 2010;Perry et al, 2008;Setlow et al, 2009). There is less known, however, regarding relationships between risk taking and drug use, particularly in the context of adolescence.…”

“…Rats in the cocaine SA group (n ¼ 28) underwent surgery at P70-75 to implant jugular catheters (as in Mendez et al (2010)-see Supplementary Information for details). Cocaine SA sessions took place in operant chambers located in a different room from those used for RDT testing.…”

Translational research into intertemporal choice: The Western scrub-jay as an animal model for future-thinking

“…Dalley et al, 2007). Similarly, animal work has offered clear insight into the effects of recent exposure to cocaine on intertemporal choice (Mendez et al, 2010;Roesch et al, 2007). Taken together, this research implicates intertemporal choice as an important component in the development and maintenance of drug addiction (Bickel et al, 2007).…”

Animal Studies of Addictive Behavior

“…Thus, high impulsivity in rats predicts the vulnerability to alcohol consumption, nicotine self-administration, cocaine selfadministration, and signs of cocaine addiction (Poulos et al 1995;Perry et al 2005;Dalley et al 2007a;Belin et al 2008;Diergaarde et al 2008), although impulsive behavior does not appear to predict heroin self-administration (McNamara et al 2010;Schippers et al 2012). Conversely, a period of self-administration of cocaine, methamphetamine, MDMA, or heroin has been shown to affect a variety of cognitive functions in rats, including attention, working memory, cognitive flexibility, object recognition memory, and impulsive behavior (Dalley et al 2005(Dalley et al , 2007bCalu et al 2007;Briand et al 2008;Rogers et al 2008;Gipson and Bardo 2009;Winstanley et al 2009;Mendez et al 2010;Parsegian et al 2011;Schenk et al 2011;Schippers et al 2012). Interestingly, some of these deficits were specifically observed (or more prominently so) in animals with a history of escalated drug taking (Briand et al 2008;George et al 2008;Rogers et al 2008;Gipson and Bardo 2009).…”