Appetitive Pavlovian conditioned approach to reward location is reduced by both adrenergic and NMDA receptor antagonism at memory reconsolidation

Abstract Rationale Appetitive Pavlovian cues can drive maladaptive reward seeking via stimulus–reward memories. Disrupting memory reconsolidation offers a potential strategy to reduce their influence, but evidence for β-adrenergic blockade with propranolol is inconsistent across behavioural paradigms, particularly relative to NMDA receptor antagonism. Objectives We tested whether propranolol disrupts reconsolidation of appetitive sucrose memories in a paradigm involving discriminative pavlovian conditioned approach to the reward location, and compared its effects with those of the most commonly used NMDA receptor antagonist, MK-801. Methods Adult Lister hooded rats underwent discriminative Pavlovian conditioning. Thirty minutes before a brief memory reminder (non-reinforced or reinforced), rats received systemic drug treatment or saline control. In study 1, MK-801 (0.1 mg/kg) was administered to male rats. In study 2, propranolol (10 mg/kg) was administered to equal numbers of male and female rats. Discriminative approach to the reward location was tested drug-free at 1 and 8 days. Results In study 1, MK-801 impaired subsequent discriminated responding at test. These effects were observed not only when reminder was non-reinforced as in previous successful demonstrations, but also with reinforced reminder. In study 2, Propranolol also impaired subsequent conditioned approach, regardless of reminder type, and the effects were consistent across sexes. Conclusions Propranolol and MK-801 can both disrupt reconsolidation of appetitive pavlovian memories under conditions that promote memory destabilisation. These findings demonstrate that β-adrenergic blockade can impair appetitive memory reconsolidation in a paradigm of conditioned approach to the reward location, challenging prior null findings and revitalising the potential for propranolol-based interventions in maladaptive reward-seeking behaviours.