PROTOCOL-DEPENDENT EFFECTS OF INFRALIMBIC LACTATE SIGNALING ON COCAINE MEMORY: EXTINCTION VERSUS RECONSOLIDATION

Drug exposure induces enduring neuroplastic changes that underlie pathological memories, which can be reactivated by drug-associated cues to trigger craving. To attenuate these cue-driven responses, extinction training (reexposure to drug-associated cues in the absence of the drug) has been proposed as a therapeutic strategy. Astrocyte-derived L-lactate functions as a signaling molecule in astrocyte–neuron communication, promoting synaptic plasticity and long-term memory, suggesting that enhancing cue extinction through L-lactate administration may reduce drug seeking. Our study investigated whether intra-infralimbic cortex L-lactate administration facilitates extinction and prevents relapse in a cocaine self-administration paradigm in rats. Additionally, we assessed the effects of this manipulation on c-Fos expression and perineuronal nets (PNNs). In Experiment 1, following a short-access cocaine training protocol, rats underwent daily 1-hour extinction sessions and received Lactate infusions at the end of each session. Drug-seeking tests were conducted 24 h, 8 days, and 15 days after the last cocaine exposure. L-lactate-treated rats displayed a higher number of active lever presses during extinction and drug-seeking sessions compared with controls. These findings suggest that L-lactate administration did not enhance extinction memory but may instead strengthen the original cocaine-associated memory, possibly by facilitating reconsolidation. To address this possibility, Experiment 2 employed a long-access cocaine training protocol to generate a more robust and extinction-resistant memory, together with extended extinction sessions (2 h). This approach allowed a clearer dissociation between potential effects of L-lactate on consolidation of the original memory versus reconsolidation of extinction learning.
Funding: PNSD 2023I069; GACUJIMB/2024/01