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

Abstract

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.

Transition from ‘model-based’ to ‘model-free’ behavioral control in addiction: Involvement of the orbitofrontal cortex and dorsolateral striatum

“…A key recent study (Shiflett, 2012) has demonstrated that drug exposure selectively enhances general PIT effects, while it abolishes specific transfer (Fig. 2a).…”

Learning and Motivational Processes Contributing to Pavlovian–Instrumental Transfer and Their Neural Bases: Dopamine and Beyond

“…For example, Corbit and Janak (2007b) trained rats in a specific PIT design with alcohol and sucrose reward and found that, whereas the sucrose stimulus generated the expected specific transfer effect, enhancing responding for sucrose but not alcohol, the same was not true for the alcohol stimulus which was found to enhance both responses in a manner reminiscent of general transfer (see also Shiflett 2012). The specificity of PIT in alcoholics, as well as the direct effects of alcohol stimuli on alcohol seeking, would be of significant interest for future study.…”

Individual variation in resisting temptation: Implications for addiction

“…Dopamine appears to be somewhat less important for the outcome-selective version of PIT. For example, Yin et al (2006) found that hyperdopaminergic mice failed to show elevated outcome-specific PIT, relative to wild type control mice (see also, Shiflett, 2012). Furthermore, Ostlund and Maidment (2012) reported that dopamine antagonists did not influence the ability of CSs to bias action selection for a specific outcome.…”