Dopamine Receptor Blockade Attenuates the General Incentive Motivational Effects of Noncontingently Delivered Rewards and Reward-Paired Cues Without Affecting Their Ability to Bias Action Selection

Abstract

Environmental cues affect our behavior in a variety of ways. Despite playing an invaluable role in guiding our daily activities, such cues also appear to trigger the harmful, compulsive behaviors that characterize addiction and other disorders of behavioral control. In instrumental conditioning, rewards and reward-paired cues bias action selection and invigorate reward-seeking behaviors, and appear to do so through distinct neurobehavioral processes. Although reward-paired cues are known to invigorate performance through a dopamine-dependent incentive motivational process, it is not known if dopamine also mediates the influence of rewards and rewardpaired cues over action selection. The current study contrasted the effects of systemic administration of the nonspecific dopamine receptor antagonist flupentixol on response invigoration and action bias in Pavlovian-instrumental transfer, a test of cue-elicited responding, and in instrumental reinstatement, a test of noncontingent reward-elicited responding. Hungry rats were trained on two different stimulus-outcome relationships (eg, tone-grain pellets and noise-sucrose solution) and two different action-outcome relationships (eg, left press-grain and right press-sucrose). At test, we found that flupentixol pretreatment blocked the response invigoration generated by the cues but spared their ability to bias action selection to favor the action whose outcome was signaled by the cue being presented. The response-biasing influence of noncontingent reward deliveries was also unaffected by flupentixol. Interestingly, although flupentixol had a modest effect on the immediate response invigoration produced by those rewards, it was particularly potent in countering the lingering enhancement of responding produced by multiple reward deliveries. These findings indicate that dopamine mediates the general incentive motivational effects of noncontingent rewards and reward-paired cues but does not support their ability to bias action selection.

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

“…Given dopamine's well-established involvement in the response-invigorating influence of reward-paired cues (Dickinson et al, 2000;Lex and Hauber, 2008;Ostlund and Maidment, 2012;Wassum et al, 2011Wassum et al, , 2013, such an interaction may be at least partially responsible for mediating the disruptive effect of mecamylamine reported here. However, this would not explain the similar disruption produced by scopolamine, given that it and other muscarinic receptor antagonists tend to facilitate dopamine signaling by blocking acetylcholine autoreceptor activity (Cachope et al, 2012;Chapman et al, 1997;Di Giovanni and Shi, 2009).…”

“…Both families of receptors are highly expressed in brain areas implicated in instrumental learning and performance, including the striatum, prefrontal cortex, and amygdala (Goldberg et al, 2012;Leslie et al, 2013;Thiele, 2013). Acetylcholine is also known to be involved in regulating dopamine signaling (Cachope et al, 2012;Chapman et al, 1997;Di Giovanni and Shi, 2009;Threlfell et al, 2012), a neuromodulator that has been more directly implicated in motivated behavior and is known to underlie the response-invigorating influence of rewardpaired cues on reward-seeking behavior (Dickinson et al, 2000;Lex and Hauber, 2008;Ostlund and Maidment, 2012;Wassum et al, 2011Wassum et al, , 2013. While acetylcholine has been implicated in various aspects of reward-motivated behavior (Mendez et al, 2012;Pratt and Kelley, 2004;Ragozzino et al, 2009), much remains unknown about its specific contributions to action selection.…”

Dopamine dependency for acquisition and performance of Pavlovian conditioned response

“…One interesting hypothesis posits that Pavlovian predictions of outcomes (rewards) underpin some types of instrumental-based control of behavior (1). One example is Pavlovian-to-instrumental transfer, in which Pavlovian cues actually modify instrumental responses (38,39). We have previously shown that vrDD-DS mice are similar to vrDD-VS mice in their ability to learn an instrumental lever-press response (19,20).…”

Translational Rodent Paradigms to Investigate Neuromechanisms Underlying Behaviors Relevant to Amotivation and Altered Reward Processing in Schizophrenia

“…46 Additionally, mice without alpha7 nAChRs exhibited normal physical effort motivation but impaired reward-associative learning, 87 despite such mice exhibiting normal learning in aversively motivated environments. 88 Other differences include the need of the dorsal striatum in rats performing an effort-based decision-making task 89,90 but not in the PRBP. 91 Future studies using specific cross-species tests and manipulations may solidify the neuromechanisms mediating these specific behaviors in both humans and rodents for as yet there remain too few studies for a complete understanding.…”