Differential involvement of dopamine receptor subtypes in the acquisition of Pavlovian sign-tracking and goal-tracking responses

Abstract

Rationale Previous work has identified that different forms of Pavlovian conditioned approach, sign-tracking and goal-tracking, are governed by distinct neurochemical mechanisms when compared in animals predisposed to learning one form vs. the other. Objectives The present study aimed to investigate whether these are also neurochemically distinct processes in a population of animals capable of developing either response when this is manipulated via the use of distinct conditioned stimuli (CS). Methods Rats were trained on one of two Pavlovian conditioning procedures in which the CS was either a lever, which elicits sign-tracking, or an auditory click, which elicits goal-tracking. The differential involvement of dopamine D1- and D2-receptors (D1R; D2R) in the acquisition of approach types was investigated via systemic administration of antagonists selective to one or both receptor subtypes during Pavlovian training. Results Results indicate that dopaminergic signalling is important for the acquisition of both sign-tracking and goal-tracking responses. However, whilst development of sign-tracking to a lever depends on activity at both D1R and D2R, development of goal-tracking in response to a click was shown to depend only on activity at D1R. Conclusions We suggest that the importance of D1R activity in both sign- and goal-tracking acquisition reflects a general role in learning Pavlovian associations, which aligns with data implicating dopamine in prediction error processes. In contrast, the selective involvement of D2R activity in sign-tracking acquisition may reflect its importance in motivational processes such as incentive salience attribution. Electronic supplementary material The online version of this article (10.1007/s00213-019-5169-8) contains supplementary material, which is available to authorized users.

Effects of dopamine receptor antagonism and amphetamine-induced psychomotor sensitization on sign- and goal-tracking after extended training

“…Antagonism of dopamine D 1 -like receptors reduced the expression of both sign- and goal-tracking conditioned responses, but these results should be interpreted with caution in the face of reduced ITI port entries and general locomotor behaviour. Interestingly, dopamine D 2 -like receptor signalling was specifically required for the expression of goal-tracking in goal-trackers, and this finding extends previous work on the effects of D 2 receptor manipulations on conditioned approach behaviour (Chow et al, 2016; Roughley and Killcross, 2019; Bédard et al, 2011). A second, parallel objective was to investigate whether the dopamine system is involved in the shift from goal- to sign-tracking behaviour resulting from extended PCA training.…”

“…Importantly, we tested the effect of eticlopride under extinction conditions (no sucrose), similar to the drug-free CS only tests used by Chow et al (2016), ensuring that any observed effects would relate specifically to performance of already-learned behaviours and would not be influenced by the reinforcer. Consistent with the interpretation of Chow et al (2016), Roughley and Killcross (2019) observed an impairment of sign-tracking, but not goal-tracking, in drug-free sessions that followed one week of daily pre-training eticlopride. The present data show that D 2 antagonism prior to testing under extinction conditions disrupts goal-tracking, which is entirely reliant on the CS-US association but leaves sign-tracking, which involves phasic dopamine responses to the CS rather than to the US (Flagel et al, 2011), intact.…”

Dopamine D2R upregulation in nucleus accumbens indirect pathway does not affect Pavlovian or Go/No-Go Learning

“…behaviors. Both D2Rs and D1Rs play an important role in sign-tracking behaviors while only the activity of D1Rs 12 is necessary for the development of goal-tracking behaviors (Roughley & Killcross, 2019). Here, our behavioral 13 paradigm limited our analysis to only measure goal-tracking behaviors, which may explain why D2R upregulation 14 did not affect Pavlovian learning.…”

Memory reconsolidation impairments in sign-tracking to an audiovisual compound stimulus

“…In the present study, the ratio of sign-trackers to goal-trackers was closer to 50:50 across all experiments. This is likely due to the fact that sign-tracking is more likely to be acquired to highly localizable visual stimuli (Robinson and Flagel 2009; Roughley and Killcross 2019), whereas goal-tracking is promoted by auditory stimuli (Roughley and Killcross 2019). Therefore, there may be individual differences in the salience attributed to, and the attention directed towards, the visual and auditory elements of our compound stimuli.…”

“…Such individual differences may be related to the emerging differential mechanisms of sign-tracking and goal-tracking behaviour (e.g. dopamine D2R activity; Roughley and Killcross 2019).…”