Psilocybin mitigates chronic behavioral and neurobiological alterations in a rat model of recurrent intimate partner violence-related brain injury.

In a rat model of recurrent intimate partner violence brain injury (daily mild traumatic brain injury plus non-fatal strangulation for five days followed by 16 weeks of recovery), a single dose of psilocybin (1 mg/kg) reversed injury-induced anxiety-like behavior in the elevated plus-maze, increased sucrose preference (indicating reduced anhedonia), and improved reversal learning in the water maze and spatial memory in the Y-maze. Psilocybin also prevented the increase in microglial cells in the dorsal hippocampal molecular layer and the loss of reelin-positive cells in the subgranular zone seen in saline-treated injured rats. Pre-treatment with a 5-HT2A receptor antagonist blocked psilocybin's behavioral effects, indicating these benefits depend on 5-HT2A receptor activation.

Study at a glance

Abstract

Intimate partner violence (IPV) poses a significant medical concern, predominantly affecting females. IPV-related brain injuries (IPV-BI), such as mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), sustained during physical attacks are common and often repetitive. Chronic neurobehavioral sequalae from IPV-BI are associated with neuroinflammation and impaired neuroplasticity, and effective treatment options are scarce, particularly in the context of IPV. However, psilocybin, a 5-HT2A receptor agonist with therapeutic potential in psychiatric disorders that share overlapping pathophysiology as BI, is a promising candidate. This study evaluated psilocybin's effects on behavior, cognition, and neurobiology in a novel rat model of recurrent IPV-BI. Female rats underwent daily mTBI (lateral impact) followed by NFS (90 s) for five days, followed by 16 weeks of recovery. Rats then received a single intraperitoneal injection of psilocybin (1 mg/kg) or saline, with behavioral testing 24 h later. To investigate whether psilocybin's effects were 5-HT2A receptor dependent, additional rats received pre-treatment with selective 5-HT2A receptor antagonist M100907 (1.5 mg/kg) one hour before psilocybin administration. Psilocybin recovered mTBI+NFS-induced abnormalities in the elevated plus-maze, increased sucrose preference when administered without M100907, and improved reversal learning in the water maze and spatial memory in the Y-maze. In the dorsal hippocampus, mTBI+NFS rats treated with saline, but not those treated with psilocybin, exhibited an increased number of microglial cells in the molecular layer and fewer reelin-positive cells in the subgranular zone. These findings suggest psilocybin's antidepressant, pro-cognitive, anti-inflammatory, and neuroplasticity-enhancing effects hold promise for improving chronic IPV-BI outcomes and highlight the critical role of 5-HT2A receptors in mediating psilocybin's therapeutic benefits.