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

Abstract

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.

Differential Effects of Systemic Cholinergic Receptor Blockade on Pavlovian Incentive Motivation and Goal-Directed Action Selection

“…Indeed, a recent transfer study found that Pavlovian cues associated with passive intravenous cocaine delivery have the ability to provoke cocaine seeking in rats (LeBlanc et al, 2012). Furthermore, studies using a food-motivated version of the transfer task have shown that rats given repeated exposure to psychostimulants exhibit heightened levels of cuetriggered food seeking (Leblanc et al, 2013a;LeBlanc et al, 2013b;Saddoris et al, 2011;Wyvell and Berridge, 2001), suggesting that these drugs cause long-lasting alterations in the neural substrates of Pavlovian incentive motivation. The current findings indicate that this behavioral influence of Pavlovian learning critically depends on cholinergic signaling through muscarinic and nicotinic receptors, suggesting that drug-induced adaptations in the cholinergic system may contribute to compulsive drug seeking by augmenting the influence of Pavlovian cues.…”

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

“…For example, as noted above, specific transfer effects are impervious to outcome devaluation, suggesting that the cuing effects of stimuli do not require that the consequences of the invigorated response be a current goal. Furthermore, transfer effects appear to grow under conditions that favor habitual responding, such as following extended training (Holland 2004) or drug exposure (Saddoris et al 2011;LeBlanc et al 2013), again providing evidence of a dissociation between the ability of stimuli to invigorate responding and an evaluative process concerned with the consequences of that responding.…”

Phasic Mesolimbic Dopamine Signaling Encodes the Facilitation of Incentive Motivation Produced by Repeated Cocaine Exposure

“…Immediately after each injection the rats were placed in the behavioral chamber used for initial training for 45 min. This cocaine administration protocol was previously shown to support locomotor sensitization and facilitate the expression of the PIT effect (LeBlanc et al, 2013b). Rats remained undisturbed in their home cages for 8 days before further behavioral testing.…”