Repeated cocaine experience facilitates sucrose-reinforced operant responding in enriched and isolated rats

Klein, Emily D.; Gehrke, Brenda J.; Green, Thomas A.; Zentall, Thomas R.; Bardo, Michael T.

doi:10.1016/j.lmot.2006.07.004

Cited by 10 publications

(10 citation statements)

References 33 publications

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“…Arguing against this possibility, however, enhanced conditioned approach was observed on the first trial of the Pavlovian reminder session, which suggests that the rats possessed an altered response to the CS prior to any re-training sessions. Unlike previous studies, no effects of amphetamine sensitization on instrumental response rates were observed (Klein et al 2007; Mendez et al 2009; Nordquist et al 2007). One possibility for this difference is that the response requirement used here was not appropriate to detect effects of amphetamine sensitization.…”

Section: Discussioncontrasting

confidence: 98%

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

Shiflett

2012

Psychopharmacology

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Rationale Repeated exposure to psychostimulants alters behavioral responses to reward-related cues; however, the motivational underpinnings of this effect have not been fully characterized. Objectives The following study was designed to examine how amphetamine sensitization affects performance in rats on a series of Pavlovian and operant tasks that distinguish between general-incentive and outcome-selective forms of conditioned responses. Methods Adult male rats underwent Pavlovian and instrumental training for food pellet rewards. Following training, rats were sensitized to d-amphetamine (2 mg/kg for 7 days). Rats were subsequently tested on an outcome-selective Pavlovian-instrumental transfer (PIT) task, an outcome-reinstatement task, and an outcome devaluation task. Additionally, in a separate experiment PIT was assessed in amphetamine-sensitized and control rats using a Pavlovian backward-conditioned stimulus. Results Repeated amphetamine exposure sensitized locomotor activity to acute amphetamine challenge. Amphetamine altered responses to CS presentations by increasing conditioned approach. During tests of PIT amphetamine-treated rats showed no outcome-selectivity in their responding, responding to a CS whether or not it shared a common outcome with the instrumental response. No effect of amphetamine sensitization was observed on tests of outcome-selective reinstatement by outcome delivery, or action selection based on outcome value. Amphetamine-sensitized rats showed impaired outcome-selective PIT to a backward CS but were unaltered in conditioned approach. Conclusions Amphetamine sensitization prevents outcome-selective responding during PIT, which is dissociable from amphetamine’s effects on conditioned approach. These data suggest fundamental alterations in how stimuli motivate action in addiction.

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Section: Discussioncontrasting

confidence: 98%

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

Shiflett

2012

Psychopharmacology

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“…The current findings add to a growing literature showing that repeated drug administration can enhance appetitive behaviors generated by non-drug rewards. [29], [30], [34]–[37], [51], [61]–[65]. Such findings suggest that extended drug exposure produces nonspecific alterations in motivation, perhaps via adaptations in the dopamine system.…”

Section: Discussionmentioning

confidence: 92%

Repeated Cocaine Exposure Facilitates the Expression of Incentive Motivation and Induces Habitual Control in Rats

2013

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There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

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“…These findings suggest a dissociation between the effects of chronic cocaine on probabilistic and delay discounting in rats, which is supported by findings in human cocaine users showing no correlation between performance on delay and probabilistic decision-making tasks (Monterosso et al, 2001), as well as by data in rats showing no correlations between performance on these two tasks (Simon, Gilbert, Mayse, Bizon, & Setlow, 2009). Furthermore, the dissociation between the effects of chronic cocaine in these two tasks suggests that the elevated impulsive choice in the delay discounting task was due primarily to cocaine’s effects on factors specific to temporal decision-making, rather than on general factors such as increases in incentive motivation, changes in sensitivity to reward magnitude, or discriminative ability, although it is possible that the longer withdrawal time at which rats were tested in the probabilistic discounting task may have reduced cocaine’s effects (Deroche, Le Moal, & Piazza, 1999; Klein, Gehrke, Green, Zentall, & Bardo, 2007; Mendez et al, 2008; Roesch et al, 2007). Interestingly, the opposite pattern of effects in these two decision-making tasks has been observed following several weeks of withdrawal from chronic experimenter-administered amphetamine, which has no effect on delay discounting but increases choice of the large uncertain reward in the probabilistic discounting task (Floresco & Whelan, 2009; Stanis, Marquez Avila, White, & Gulley, 2008)—note that although increases in impulsive choice have been observed during chronic amphetamine administration, these effects do not endure for more than a few days of withdrawal (Gipson & Bardo, 2009).…”

Section: Discussionmentioning

confidence: 99%

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

Mendez

Simon

Hart

et al. 2010

Behavioral Neuroscience

117

103

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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.

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Repeated cocaine experience facilitates sucrose-reinforced operant responding in enriched and isolated rats

Cited by 10 publications

References 33 publications

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

The effects of amphetamine exposure on outcome-selective Pavlovian-instrumental transfer in rats

Repeated Cocaine Exposure Facilitates the Expression of Incentive Motivation and Induces Habitual Control in Rats

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

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