Dissociable hippocampal and amygdalar D1-like receptor contribution to discriminated Pavlovian conditioned approach learning

Abstract

Pavlovian conditioning is an elementary form of reward-related behavioral adaptation. The mesolimbic dopamine system is widely considered to mediate critical aspects of reward-related learning. For example, initial acquisition of positively-reinforced operant behavior requires dopamine (DA) D1 receptor (D1R) activation in the basolateral amygdala (BLA), central nucleus of the amygdala (CeA), and the ventral subiculum (vSUB). However, the role of D1R activation in these areas on appetitive, non-drug-related, Pavlovian learning is not currently known. In separate experiments, microinfusions of the D1-like receptor antagonist SCH-23390 (3.0 nmol/0.5 μL per side) into the amygdala and subiculum preceded discriminated Pavlovian conditioned approach (dPCA) training sessions. D1-like antagonism in all three structures impaired the acquisition of discriminated approach, but had no effect on performance after conditioning was asymptotic. Moreover, dissociable effects of D1-like antagonism in the three structures on components of discriminated responding were obtained. Lastly, the lack of latent inhibition in drug-treated groups may elucidate the role of D1-like in reward-related Pavlovian conditioning. The present data suggest a role for the D1 receptors in the amygdala and hippocampus in learning the significance of conditional stimuli, but not in the expression of conditional responses.

The Contribution of the Amygdala to Reward-Related Learning and Extinction

“…If the CeA is involved in discriminating positive or negative reward value (discussed below), CeA inactivation may impair this discrimination, leading to a lower discrimination score. Supporting this interpretation, Andrzejewski and colleagues reported equal nose poking rates between the CS+ and CS−, rather than an abolition of nose poking [15], which would support lack of discrimination between the two CSs but not an inhibition of nose poking following CeA inactivation. It is also possible that these effects relate specifically to dopamine function within the CeA.…”

“…Inactivation of the BLA with the NMDA antagonists AP-5 or d,l-2-2-amino-5-phosphonovalerate (D-APV) impairs acquisition, but not expression of Pavlovian conditioned approach for sucrose or taste potentiated odour aversion [13,14], while inhibition of dopamine D 1 receptor activity with SCH-23390 impairs acquisition of Pavlovian discriminative stimulus responding (i.e. approaching the food cup in the presence of a CS+, but not a CS−) [15]. D 1 antagonism has no effect on responding when animals are trained further and tested drug free, suggesting a specific role for BLA D 1 receptors in the performance of Pavlovian discriminative stimulus approach [15].…”

“…approaching the food cup in the presence of a CS+, but not a CS−) [15]. D 1 antagonism has no effect on responding when animals are trained further and tested drug free, suggesting a specific role for BLA D 1 receptors in the performance of Pavlovian discriminative stimulus approach [15]. It appears acquisition of Pavlovian associations rely on a BLA to nucleus accumbens (NAcc) pathway, as optogenetic inactivation of the BLA to NAcc pathway using halorhodopsin impairs acquisition of licking behaviour for sucrose in response to sucrose predictive cues ( [16], see also Ref.…”

“…In Pavlovian approach paradigms, each CS+ is associated with a reinforcer, but not with the absence of reinforcement. CeA lesions or intra-CeA inactivation of D 1 or D 3 receptors reduces conditioned approach behaviour [15,83,84]. If the CeA is involved in discriminating positive or negative reward value (discussed below), CeA inactivation may impair this discrimination, leading to a lower discrimination score.…”

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

“…The possibility that US-approach behaviour in sign-tracking animals might be better defined as “sign-tracking to the goal” may help explain findings indicating the involvement of dopamine in Pavlovian acquisition where the conditioned response measured was approach to the food magazine (Andrzejewski and Ryals 2016; Darvas et al 2014; Eyny and Horvitz 2003), which would otherwise contradict the notion that dopamine is not necessary for acquisition of goal-tracking (Flagel et al 2011). In addition, it is important to explore this question more directly for the purposes of research that seeks to increase our understanding of associative learning processes in general, as well as that which makes use of the sign-tracking/goal-tracking paradigm for modelling aspects of emotional and motivational disorders like addiction.…”