Activation of Group II Metabotropic Glutamate Receptors in the Basolateral Amygdala Inhibits Reward Seeking Triggered by Discriminative Stimuli

Reward-associated cues are essential in guiding reward-seeking behaviours. These cues include conditioned stimuli (CSs) which occur following seeking actions and indicate reward delivery, and discriminative stimuli (DSs) which occur response-independently and signal reward availability. 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. We first 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 first self-administered sucrose during sessions where discriminative stimuli signaled periods of sucrose availability (DS+) and unavailability (DS-). During DS+ presentations, active lever presses produced sucrose paired with a CS+. During DS-presentations, active lever presses produced a CS- and no sucrose. Across 14 sessions, rats learned to load up on sucrose during DS+ presentation and inhibit responding during DS-presentation. We then compared the effects of intra-BLA microinfusions of the mGlu2/3 receptor agonist LY379268 on cue-evoked sucrose seeking during an extinction test (no sucrose) where the DSs and CSs were presented response-independently. Before test, rats received intra-BLA microinjections of artificial cerebrospinal fluid (aCSF) or LY379268. Under aCSF, only the DS+ and DS+CS+ combined triggered increases in reward-seeking behaviour. The CS+ alone was ineffective. Intra-BLA LY379268 reduced sucrose seeking triggered by the DS+ and DS+CS+ combination. Thus, 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.