Faecal Microbiota Transplantation Modulates Morphine Addictive-Like Behaviours Through Hippocampal Metaplasticity

Abstract

The microbiota-gut-brain axis has been implicated in the pathology of substance use disorders (SUDs). In light of the brain's capability to reorganize itself in response to intrinsic and extrinsic stimuli, opioid-induced dysbiosis is likely to contribute to addictive behaviour through modulating neuroplasticity. In this study, a faecal microbiota transplantation (FMT) from a saline-donor was performed on morphine-treated rats to evaluate the effects of gut microbiota on morphine-induced metaplasticity and addictive behaviours. Male Wistar rats were treated with subcutaneous injections of 10 mg/kg morphine sulphate every 12 h for 9 days in an effort to induce dependence. The withdrawal syndrome was precipitated by injecting naloxone (1.5 mg/kg, ip) after the final dose of morphine. The tolerance was induced by repeated morphine injections over a period of 7 days (10 mg/kg, once a day, ip). FMT was applied daily through gavage of processed faeces 1 week before and during the morphine treatment. Field potential recordings (i.e., fEPSP) were carried out to assess short-term and long-term synaptic plasticity in the CA1 area of the hippocampus following Schaffer-collateral stimulation. Animals subjected to FMT exhibited significant reductions in naloxone-precipitated withdrawal syndrome (one-way ANOVA, p < 0.05). Tolerance to the analgesic effects of morphine was not affected by FMT (two-way ANOVA, p > 0.05). Following high-frequency stimulation (HFS) to induce long-term potentiation (LTP), a greater fEPSP slope was observed in morphine-treated animals (unpaired t test, p < 0.05). FMT from saline-donor rats diminished morphine-induced augmented LTP (unpaired t test, p < 0.05). These results highlighted the alleviating effects of FMT from saline-donors on morphine-induced metaplasticity and dependence potentially by modulating the dysbiosis of gut microbiota.

Keywords: dependence; gut microbiota; gut–brain axis; hippocampus; opioid addiction; synaptic plasticity.