Acute psilocybin increased cortical activities in rats

Junhong Liu; Yuanyuan Wang; Ke Xia; Jinfeng Wu; Danhao Zheng; Aoling Cai; Haitao Yan; Ruibin Su

doi:10.3389/fnins.2023.1168911

Acute psilocybin increased cortical activities in rats

Front Neurosci. 2023 May 23:17:1168911. doi: 10.3389/fnins.2023.1168911. eCollection 2023.

Authors

Junhong Liu¹, Yuanyuan Wang^{1

2}, Ke Xia¹, Jinfeng Wu³, Danhao Zheng³, Aoling Cai⁴, Haitao Yan¹, Ruibin Su¹

Affiliations

¹ State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Key Laboratory of Neuropsychopharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
² Nanjing University of Chinese Medicine, Nanjing, China.
³ State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, Hubei, China.
⁴ The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.

Abstract

Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate psilocybin-induced changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocybin on rats have not been carefully investigated. This study aimed to explore how psilocybin affects resting-state brain activity and FC, through a combination of BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocybin hydrochloride injection (2.0 mg/kg, i.p.), positive brain activities were observed in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. And a region-of-interest (ROI) -wise FC analysis matrix suggested increased interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex within the cortical and striatal areas. Consistently, acute psilocybin increased the EGR1 level throughout the brain, indicating a consistent activation thought the cortical and striatal areas. In conclusion, the psilocybin-induced hyperactive state of rats is congruent to that of humans, and may be responsible for its pharmacological effects.

Keywords: 5-HT2A; BOLD; EGR1 (early growth response protein 1); depression; fMRI; functional connectivity (FC); psilocybin; psychedelics.