Naloxone reversed cognitive impairments induced by repeated morphine under heavy perceptual load in the 5-choice serial reaction time task

Repeated opioids abuse may produce long-lasting and complicated cognitive deficits in individuals. Naloxone is a typical mu-opioid receptor antagonist widely used in clinical treatment for opioid overdose and opioid abuse. However, it remains unclear whether naloxone affects morphine-induced cognitive deficits. Using the 5-choice serial reaction time task (5-CSRTT), the present study investigated cognitive profiles including attention, impulsivity, compulsivity, and processing speed in repeated morphine-treated mice. Repeated morphine administration (10 mg/kg, i.p.) induced complex cognitive changes including decreased attention and increased impulsivity, compulsivity, processing speed. Systemic naloxone administration (5 mg/kg, i.p.) reversed these cognitive changes under the heavy perceptual load in 5-CSRTT. Using the novel object recognition (NOR), Y-maze and open-field test (OFT), the present study investigated the memory ability and locomotor activity. Naloxone reversed the effect of morphine on recognition memory and locomotion but had no effect on working memory. In addition, repeated morphine administration decreased the expression of postsynaptic density protein 95 (PSD95) and cAMP response element binding protein (CREB) phosphorylation in the prefrontal cortex (PFC) and hippocampus (HIP), and these effects were significantly reversed by naloxone in PFC. Our study suggests that repeated exposure to morphine affects multiple cognitive aspects and impairs synaptic functions. Systemic naloxone treatment reverses the mu-opioids-induced cognitive changes, especially under the heavy perceptual load, possibly by restoring the synaptic dysfunctions.