1 Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
2 Neural Signaling and Circuitry Research Group (SNC), Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
3 Center for Biomedical Innovation (CIB), Université de Montréal, Montréal, QC, Canada.
4 Center for Interdisciplinary Research on the Brain and Learning (CIRCA), Université de Montréal, Montréal, QC, Canada.
5 Center for Studies in Behavioural Neurobiology, Concordia University, Montréal, QC, Canada.

Background: Reward-associated cues guide reward-seeking behaviours. These cues include conditioned stimuli (CSs), which occur following seeking actions and predict reward delivery, and discriminative stimuli (DSs), which occur response-independently and signal that a seeking action will produce reward. Metabotropic group II glutamate (mGlu2/3) receptors in the basolateral amygdala (BLA) modulate CS-guided reward seeking; however, their role in DS effects is unknown.

Methods: We developed a procedure to assess DS and CS effects on reward seeking in the same subjects within the same test session. Female and male rats self-administered sucrose where DSs signaled periods of sucrose availability (DS+) and unavailability (DS-). During DS+ trials, active lever presses produced sucrose paired with a CS+. During DS- trials, active lever presses produced a CS- and no sucrose. Across 14 sessions, rats learned to load up on sucrose during DS+ trials and inhibit responding during DS- trials. We then compared the effects of intra-BLA microinfusions of the mGlu2/3 receptor agonist LY379268 on cue-evoked sucrose seeking during a test where the DSs and CSs were presented response-independently, without sucrose. Before testing, rats received intra-BLA microinjections of artificial cerebrospinal fluid (aCSF) or LY379268.

Results: Under aCSF, only the DS+ and DS+CS+ combined triggered increases in reward-seeking behaviour. The CS+ alone was ineffective. Intra-BLA LY379268 reduced the sucrose seeking triggered by the DS+ and DS+CS+ combination.

Conclusions: Using a new procedure to test reward seeking induced by DSs and CSs, we show that BLA mGlu2/3 receptor activity mediates the conditioned incentive motivational effects of reward-predictive DSs.