Modulation of memory consolidation by unconditioned and conditioned opioid withdrawal: Role of stress-sensitive amygdalar circuits

This talk presents evidence that both unconditioned and conditioned opioid withdrawal enhance memory consolidation through shared neurobiological mechanisms centered on the central amygdala (CeA) and corticotropin-releasing factor (CRF) signaling. Using the object recognition task in rats (Sprague-Dawley), we have found that withdrawal — either pharmacologically precipitated or conditioned — enhanced memory when it occurred immediately after learning. These effects were paralleled by increased c-Fos expression in the CeA, and were blocked by intra-CeA infusions of a CRF1 receptor antagonist (antalarmin), indicating a causal role for CRF activity in this region. Noradrenergic signaling was also implicated, as the α2-adrenergic agonist lofexidine reversed withdrawal-induced memory enhancement. Conditioned withdrawal, established through place conditioning, similarly activated the CeA and relied on CRF signaling to influence memory consolidation. These findings suggest that withdrawal states can strengthen memory traces via stress-sensitive amygdalar circuits, potentially reinforcing drug-cue associations and contributing to the relapsing nature of opioid addiction.

Hybrid Zoom link:  https://utoronto.zoom.us/j/86328669091