Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. We hypothesized that psilocybin would show a dose-dependen...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2025.1554049/full |
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| author | Evan Fuini Arnold Chang Richard J. Ortiz Richard J. Ortiz Taufiq Nasseef Josh Edwards Marc Latta Elias Gonzalez Taylor J. Woodward Bryce Axe Ashwath Maheswari Noah Cavallaro Heather B. Bradshaw Praveen P. Kulkarni Craig F. Ferris Craig F. Ferris |
| author_facet | Evan Fuini Arnold Chang Richard J. Ortiz Richard J. Ortiz Taufiq Nasseef Josh Edwards Marc Latta Elias Gonzalez Taylor J. Woodward Bryce Axe Ashwath Maheswari Noah Cavallaro Heather B. Bradshaw Praveen P. Kulkarni Craig F. Ferris Craig F. Ferris |
| author_sort | Evan Fuini |
| collection | DOAJ |
| description | Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. We hypothesized that psilocybin would show a dose-dependent increase in activity in the prefrontal cortex and thalamus, while decreasing hippocampal activity. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. These levels were validated by measuring psilocybin and its metabolite, psilocin. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection. All data were registered to rat 3D MRI atlas with 169 brain areas providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Males and females showed different sensitivity to psilocybin dose, with females exhibiting greater activation than males at 0.3 mg/kg, especially in thalamic and basal ganglia regions. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli, such as the cortico-striato-thalamo-cortical circuit and the claustrum, showed increased activation at higher doses of psilocybin. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature. |
| format | Article |
| id | doaj-art-74fd6c3596bb4df88e6a3c867bd803e1 |
| institution | DOAJ |
| issn | 1662-453X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj-art-74fd6c3596bb4df88e6a3c867bd803e12025-08-20T03:14:01ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-05-011910.3389/fnins.2025.15540491554049Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake ratsEvan Fuini0Arnold Chang1Richard J. Ortiz2Richard J. Ortiz3Taufiq Nasseef4Josh Edwards5Marc Latta6Elias Gonzalez7Taylor J. Woodward8Bryce Axe9Ashwath Maheswari10Noah Cavallaro11Heather B. Bradshaw12Praveen P. Kulkarni13Craig F. Ferris14Craig F. Ferris15Department Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesCenter for Translational Neuroimaging, Northeastern University, Boston, MA, United StatesDepartment of Chemistry & Biochemistry, New Mexico State University, Las Cruces, NM, United StatesDepartment of Psychology, Northern Illinois University, DeKalb, IL, United StatesDepartment of Mathematics, College of Science & Humanity Studies, Riyadh, Saudi ArabiaDepartment Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesDepartment Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesDepartment Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesPsychological & Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, IN, United StatesDepartment Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesDepartment Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesDepartment Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesPsychological & Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, IN, United StatesCenter for Translational Neuroimaging, Northeastern University, Boston, MA, United StatesCenter for Translational Neuroimaging, Northeastern University, Boston, MA, United StatesDepartment Psychology & Pharmaceutical Sciences, Northeastern University, Boston, MA, United StatesPsilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. We hypothesized that psilocybin would show a dose-dependent increase in activity in the prefrontal cortex and thalamus, while decreasing hippocampal activity. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. These levels were validated by measuring psilocybin and its metabolite, psilocin. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection. All data were registered to rat 3D MRI atlas with 169 brain areas providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Males and females showed different sensitivity to psilocybin dose, with females exhibiting greater activation than males at 0.3 mg/kg, especially in thalamic and basal ganglia regions. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli, such as the cortico-striato-thalamo-cortical circuit and the claustrum, showed increased activation at higher doses of psilocybin. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.https://www.frontiersin.org/articles/10.3389/fnins.2025.1554049/fullpsilocincerebellar nucleiBOLD resting state functional connectivity5-HT2A receptorhyperconnectivity |
| spellingShingle | Evan Fuini Arnold Chang Richard J. Ortiz Richard J. Ortiz Taufiq Nasseef Josh Edwards Marc Latta Elias Gonzalez Taylor J. Woodward Bryce Axe Ashwath Maheswari Noah Cavallaro Heather B. Bradshaw Praveen P. Kulkarni Craig F. Ferris Craig F. Ferris Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats Frontiers in Neuroscience psilocin cerebellar nuclei BOLD resting state functional connectivity 5-HT2A receptor hyperconnectivity |
| title | Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats |
| title_full | Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats |
| title_fullStr | Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats |
| title_full_unstemmed | Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats |
| title_short | Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats |
| title_sort | dose dependent changes in global brain activity and functional connectivity following exposure to psilocybin a bold mri study in awake rats |
| topic | psilocin cerebellar nuclei BOLD resting state functional connectivity 5-HT2A receptor hyperconnectivity |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2025.1554049/full |
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