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Kimbrough, 2021 Characterization of the brain functional architecture of psychostimulant withdrawal using single-cell whole brain imaging


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Tom2020's summary: mice in withdrawal from nicotine, methamphetamine and cocaine all showed reduced brain modularity, i.e. larger groups of brain regions activated together than in mice not in withdrawal. "Reduced modularity has been shown in several brain disorders, including traumatic brain injury, and dementia, and may be the common link between drugs of abuse."

 

eNeuro 2021 Sep 27;ENEURO.0208-19.2021. doi: 10.1523/ENEURO.0208-19.2021. Online ahead of print.
Characterization of the brain functional architecture of psychostimulant withdrawal using single-cell whole brain imaging
Adam Kimbrough, Marsida Kallupi, Lauren C Smith, Sierra Simpson, Andres Collazo, Olivier George

 

Abstract

Numerous brain regions have been identified as contributing to withdrawal behaviors, but unclear is the way in which these brain regions as a whole
lead to withdrawal. The search for a final common brain pathway that is involved in withdrawal remains elusive. To address this question, we implanted osmotic minipumps containing either saline, nicotine (24 mg/kg/day), cocaine (60 mg/kg/day), or methamphetamine (4 mg/kg/day) for 1 week in male C57BL/6J mice. After 1 week the minipumps were removed and brains collected 8 hours (saline, nicotine and cocaine) or 12 hours (methamphetamine) after removal. We then performed single-cell whole-brain imaging of neural activity during the withdrawal period when brains were collected. We used hierarchical clustering and graph theory to identify similarities and differences in brain functional architecture. Although methamphetamine and cocaine shared some network similarities, the main common neuroadaptation between these psychostimulant drugs was a dramatic decrease in modularity, with a shift from a cortical- to subcortical-driven network, including a decrease in total hub brain regions. These results demonstrate that psychostimulant withdrawal produces the drug-dependent remodeling of functional architecture of the brain and suggest that the decreased modularity of brain functional networks and not a specific set of brain regions may represent the final common pathway associated with withdrawal.

Significance Statement A key aspect of treating drug abuse is understanding similarities and differences of how drugs of abuse affect the brain. In the present study we examined how the brain is altered during withdrawal from psychostimulants. We found that each drug produced a unique pattern of activity in the brain, but that brains in withdrawal from cocaine and methamphetamine shared similar features. Interestingly, we found the major common link between withdrawal from all psychostimulants, when compared to controls, was a shift in the broad organization of the brain in the form of reduced modularity. Reduced modularity has been shown in several brain disorders, including traumatic brain injury, and dementia, and may be the common link between drugs of abuse.

 

Keywords: Addiction; Functional Connectivity; Graph Theory; Neural Activity; Withdrawal; iDISCO.

 

https://pubmed.ncbi.nlm.nih.gov/34580158/

  • 1995-present: on and off various antidepressants, and many changes in dose. Never tapered properly
  • 2012-present: citalopram. Steady dose of 27.5mg since July 2020
  • 2020: pregabalin for 2 months. Very bad withdrawal.
  • Current daily medications: 27.5mg citalopram. 1mg melatonin, 4mg doxazosin, 300mg docusate.
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