Intake-dependent effects of cocaine self-administration on impulsive choice in a delay discounting task.

Abstract

Cocaine use is associated with high levels of impulsive choice (greater discounting of delayed rewards) in humans, but the cause/effect relationships between cocaine use and impulsive choice are not fully understood. In previous work, we found that both experimenter- and self-administration of fixed quantities of cocaine caused lasting increases in impulsive choice in rats. The present study extended these findings by taking into account baseline impulsive choice prior to self-administration, and by allowing rats free access to cocaine. Male Long-Evans rats were trained in a delay discounting task in which they made discrete-trial choices between small immediate and large delayed food rewards. Half of the rats were then implanted with intravenous catheters and, following recovery, allowed to self-administer cocaine HCl (1.0 mg/kg/infusion) in 6 hour sessions over 14 days. Control rats orally self-administered a sucrose solution under similar conditions. Upon completion of self-administration training, rats remained abstinent for 3 weeks before retesting in the delay discounting task. Cocaine and control groups did not differ prior to self-administration, but afterward, the cocaine group showed greater impulsive choice (fewer choices of large, delayed rewards) than controls. Additional analyses revealed that the effects of cocaine on impulsive choice were intake-dependent; rats classified as “low intake” did not differ from controls, whereas rats classified as “high intake” were significantly more impulsive than both controls and their pre-cocaine baseline. These findings are consistent with the idea that cocaine-induced, pharmacologically based neural adaptations promote the development of impulsive decision making.

Recent Insights into the Neurobiology of Impulsivity

“…Alterations in delay discounting are often studied after acute drug exposure; however, cocaine administration may cause long-lasting elevations in impulsive choice as measured by delay discounting [27, 147, 148], a finding consistent with the human literature mentioned above. Perhaps the most compelling evidence for long-term alterations in impulsive choice as a result of cocaine exposure is in rhesus monkeys.…”

“…Greater discounting of the large reward (e.g. steeper discounting) is indicative of a more impulsive animal [26, 27]. …”

Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone

“…One issue is that treatments that reduced impulsivity led to an increased preference for the large cocaine alternative, which typically would result in increased drug intake, which was observed in males in the present study (see Figure 3). Another difficulty is that the reduction in impulsive choice observed here was due to the drug treatments interacting with the behaviorally disruptive (Smethells and Carroll 2015) or impulsivity-increasing effects of acute and chronic cocaine exposure (e.g., Broos et al 2012a; Dandy and Gatch 2009; Mitchell et al 2014; Simon et al 2007; but see Winstanley et al 2007). Regardless of these issues, the reduction in impulsive choice for cocaine provides support for employing the present treatments given the strong relationship between drug abuse and impulsive choice (see Madden and Bickel, 2010, for a review).…”

Sex differences in animal models of decision making

“…Anorexia nervosa is 13 times more prevalent in females than males (McCarthy et al 2012) and is associated with pathological risk aversion (Kaye et al 2013). Finally, there are considerable sex differences in SUD (Becker et al 2012; Carroll et al 2004; Lynch 2006), which has been shown in both preclinical and human studies to be associated with increased impulsive choice and risk-taking behavior (Anker et al, 2009; Bechara et al 2001; Gowin et al 2013; Mitchell et al 2014a; Mitchell et al 2014b). Thus, differences in decision-making between males and females could be linked to each sex’s predisposition to specific psychiatric conditions.…”