Antibiotic treatment improves gut dysbiosis and depression-like behavior induced by morphine withdrawal.

Opioid withdrawal poses a significant neuropsychiatric challenge, notably contributing to the onset of depression. Depression intertwines with gut flora richness and diversity, frequently coinciding with synaptic plasticity alterations in the brain. Gut microbiota dysbiosis potentially contributes to withdrawal-triggered depression via gut-brain axis. This research delves into the impact of antibiotic-induced gut microbiota alteration on behavioral and synaptic protein variations in mice subjected to morphine withdrawal-induced depression. A murine model was established using escalating doses of morphine followed by naloxone-precipitated withdrawal. Depression-like behaviors were assessed through tail suspension, sucrose preference, forced swimming tests, while histopathology evaluated ileocolonic inflammation. Synaptic markers, Synaptophysin (SYP) and Synapsin 1 (SYN1), in the hippocampus were analyzed via Western blotting, and gut microbiota composition was assessed through 16S rRNA sequencing. An antibiotic intervention model was employed to explore microbiota-dependent mechanisms. Morphine withdrawal induced characteristic depression-like behaviors, including prolonged immobility in forced swimming and reduced sucrose preference. Microbiota diversity metrics demonstrated significant declines in α-diversity. Histological analysis revealed marked inflammatory infiltration in ileal tissues, accompanied by reduction in hippocampal SYP expression. Antibiotic administration attenuated behavioral impairments, mitigated gut dysbiosis, reduced intestinal inflammation, and partially rescued SYP expression. These findings establish that morphine withdrawal induces intestinal dysbiosis, hippocampal synaptic plasticity deficits and depression-like behaviors, which are reversible through microbiota modulation. The results highlight the antibiotic treatment as a potential therapy for opioid withdrawal sequelae.