4.4 Article

Endocannabinoid signaling of homeostatic status modulates functional connectivity in reward and salience networks

Journal

PSYCHOPHARMACOLOGY
Volume 239, Issue 5, Pages 1311-1319

Publisher

SPRINGER
DOI: 10.1007/s00213-021-05890-z

Keywords

Endocannabinoids; Resting-state functional connectivity; Homeostatic status; Hypothalamus; Striatum; Insula; Anterior cingulate cortex

Funding

  1. NHMRC [1140197]
  2. ARC Grant [DP180100145]
  3. MRFF Next Generation of Clinical Researchers Fellowship [MRF1141214]
  4. PERIS postdoctoral contract from the Department of Health of the Generalitat de Catalunya [SLT006/17/00236]
  5. Miguel Servet contract [CP20/00165]
  6. National Health and Medical Research Council of Australia [1140197] Funding Source: NHMRC

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The study found that peripheral AEA concentrations are sensitive to homeostatic changes and correlated with neural communication in reward and salience networks. These findings have significant implications for understanding normal and abnormal interactions between homeostatic input and reward valuation.
Rationale Endocannabinoids are well poised to regulate crosstalk between energy sensing of hunger and satiety and reward-driven motivation. Objectives Here, we aimed to unravel associations between plasma endocannabinoids and brain connectivity in homeostatic and reward circuits across hunger and satiety states. Methods Fifteen participants (7 females) underwent two counter-balanced resting-state functional magnetic resonance imaging scans, one after overnight fasting and one after consumption of a standardized filling meal (satiety). Before each scan, we drew blood to measure plasma endocannabinoid concentrations (anandamide [AEA], anandamide-derived POEA, and 2-arachidonoylglycerol [2-AG]), analyzed with liquid chromatography tandem mass spectrometry. Results We found that AEA levels were associated with increased connectivity between the lateral hypothalamus and the ventral striatum during satiety. Furthermore, fasting AEA levels correlated with connectivity between the ventral striatum and the anterior cingulate cortex and the insula. Conclusions Altogether, results suggest that peripheral AEA concentrations are sensitive to homeostatic changes and linked to neural communication in reward and salience networks. Findings may have significant implications for understanding normal and abnormal interactions between homeostatic input and reward valuation.

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