Systemic opioid receptor antagonism blocks swim stress-induced retention impairment independently from CA1 and BLA opioidergic pathways

Abstract

Aims The basolateral amygdale (BLA) and dorsal hippocampus (CA1) are critical sites in mediating the effects of stress hormones on memory formation. Severe stress exposure induces memory impairment probably through activating inhibitory modulatory mechanisms such as opioidergic pathways. However, the detailed mechanisms and effect sites are not well understood. The present study was designed to investigate whether opioidergic agents, specifically in the BLA and CA1, are implicated in memory impairment induced by stressful situations. Main methods Rats carrying bilateral cannulae aimed at the BLA or CA1 were trained in a step-through passive-avoidance task and immediately were exposed to a forced swim (SW) stress (10 min, 20 °C). Retention was assessed 24 h after the training session after the animals had received a systemic or microinjection of naltrexone (a classical opioid antagonist) into the BLA/CA1 before training. Key findings The systemic administration of naltrexone (0.5, 1.5, and 3 mg/kg) blocked SW stress-induced memory impairment in a dose-dependent manner, while the microinjection into the BLA (5, 10, and 20 μg/rat) or CA1 (5, 10, and 20 μg/site) exhibited no effect on the disruptive pattern. Significance These findings, albeit confirming the role of opioidergic agents in stress-induced memory impairment, rule out the involvement of the BLA and CA1 in this effect. Future studies are needed to evaluate the opioidergic sites which mediate the disruptive effects of stress exposure on memory formation.