Dopamine D1 and D2 receptors in the nucleus accumbens core and shell mediate Pavlovian-instrumental transfer

Abstract

Pavlovian stimuli previously paired with food can markedly elevate the rate of food-reinforced instrumental responding. This effect, termed Pavlovian-instrumental transfer (PIT), depends both on general activating and specific cueing properties of Pavlovian stimuli. Recent evidence suggests that the general activating properties of Pavlovian stimuli are mediated by mesoaccumbens dopamine systems; however, the role of NAC dopamine D1 and D2 receptors is still unknown. Here we examined the effects of a selective dopamine D1 and D2 receptor blockade in the shell and core subregion of the NAC on general PIT. Rats were trained to press a single lever for food, and the effect of a single Pavlovian stimulus previously associated with the same food on performance of that lever was measured in extinction. Results reveal that PIT, that is, the increase in instrumental responding during presentation of the Pavlovian stimulus, was reduced by microinjections of the dopamine D1 receptor antagonist SCH-23390 and, less pronounced, by microinjections of the dopamine D2 receptor antagonist raclopride into the NAC core or shell, respectively. Our data suggest that dopamine D1 and D2 receptors in the NAC core and shell mediate the general activating effects of Pavlovian stimuli on instrumental behavior.

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.…”

Nucleus Accumbens Acetylcholine Receptors Modulate Dopamine and Motivation

“…Activating mAChR autoreceptors on striatal cholinergic interneurons, which can decrease acetylcholine tone at nAChRs on dopamine terminals, can also augment terminal dopamine release to high-frequency stimulation (Shin et al, 2015;Threlfell et al, 2010). Not only is it well established that reward-predictive cues trigger burst firing in dopamine cells (Schultz, 2001), but there is growing evidence that the resulting dopamine release in the NAc mediates cue-motivated instrumental behavior (Lex and Hauber, 2008;Ostlund et al, 2014b;Peciña and Berridge, 2013). Combined, these data suggest that blockade of nAChR could enhance the dopamine response to reward-predictive cues, whereas antagonizing mAChRs could blunt it.…”

“…The behavioral effects of NAc nAChR and mAChR inactivation were complimented by data showing a corresponding influence of these treatments to enhance or attenuate, respectively, cue onset-evoked NAc dopamine signaling, which has been both correlated with (Aitken et al, 2016;Ostlund et al, 2014b;Wassum et al, 2013) and causally implicated in (Lex and Hauber, 2008;Peciña and Berridge, 2013;Wyvell and Berridge, 2000) the motivating influence of cues over reward-seeking activity. Of note, under control conditions, dopamine was found to be elevated at CS + onset and to return to baseline within~30 s, similar to our recent report (Aitken et al, 2016), but shorter-lasting than the cueevoked dopamine response detected during PIT in the earlier work (Wassum et al, 2013).…”

The role of learning-related dopamine signals in addiction vulnerability

“…Interpreted in the RL framework, this suggests that the opportunity cost might be preferentially mediated via tonic dopamine in those animals that rely on model-free learning whereas the timing and vigour of model-based choices might be more directly linked to the anticipated outcome, and hence less sensitive to such tonic dopaminergic mechanisms. Indeed, interference with DA by pharmacological means or by VTA inactivation abolish the ability of Pavlovian CSs to motivate approach and produce PIT (Wassum et al, 2011;Murschall and Hauber, 2006;Lex and Hauber, 2008), and DA stimulation promotes it (Wyvell and Berridge, 2000); whereas model-based behaviour is often rather more resilient to DA manipulations (e.g. Wassum et al 2011; though see Wunderlich et al 2012b;Guitart-Masip et al 2013).…”