Effects of acute Δ9-tetrahydrocannabinol on next-day extinction recall is mediated by post-extinction resting-state brain dynamics

NEUROPHARMACOLOGY

卷:143

Article

Rabinak, Christine A.^1,2,3,4  Peters, Craig¹  Marusak, Hilary A.¹  Ghosh, Samiran^5,6,7  Phan, K. Luan^8,9,10,11 

[1] Wayne State Univ, Pharm Practice, Detroit, MI 48201 USA

[2] Wayne State Univ, Psychiat & Behav Neurosci, Detroit, MI 48201 USA

[3] Wayne State Univ, Pharmaceut Sci, Detroit, MI 48201 USA

[4] Wayne State Univ, Translat Neurosci Program, Detroit, MI 48201 USA

[5] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA

[6] Wayne State Univ, Family Med, Detroit, MI 48201 USA

[7] Wayne State Univ, Publ Hlth Sci, Detroit, MI 48201 USA

[8] Univ Illinois, Psychiat, Chicago, IL 60608 USA

[9] Univ Illinois, Psychol & Anat & Cell Biol, Chicago, IL 60608 USA

[10] Univ Illinois, Grad Program Neurosci, Chicago, IL 60608 USA

[11] Jesse Brown Med Ctr, Mental Hlth Serv Line, Chicago, IL 60612 USA

关键词: Extinction;    Cannabinoid;    Resting-state functional connectivity;    Amygdala;    Hippocampus;    Ventromedial prefrontal cortex;   

DOI  :  10.1016/j.neuropharm.2018.10.002

来源: Elsevier

【 摘 要 】

We have previously demonstrated that an acute dose of Delta 9-tetrahydrocanninbinol (THC), administered prior to extinction leaming, facilitates later recall of extinction learning and modulates the underlying neural circuitry, including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala (AMYG). It remains unknown whether THC-induced changes in fear-extinction neural circuitry can be detected following extinction learning, which may reflect ongoing processes involved consolidation of the extinction memory. To address this gap, we used a randomized, double-blind, placebo-controlled, between-subjects design to compare acute pharmacological effects of THC (7.5 mg) vs. placebo (PBO) on post-extinction resting-state functional connectivity (RS-FC) within fear-extinction circuitry in 77 healthy adults (THC = 40; PBO = 37). RS-FC was examined between vmPFC, HPC, and AMYG using two complementary approaches: 1) static RS-FC (average correlation in ROI-ROI pairs across the entire scan); and 2) dynamic (i.e., time-varying) RS-FC (sliding window correlation time series' variance). RS-FC was then linked to behavioral and brain measures of extinction recall. Compared to PBO, THC administration was associated with lower AMYG-HPC static RS-FC, but higher AMYG-vmPFC dynamic RS-FC. Lower AMYG-HPC static RS-FC was associated with higher HPC activation, as well as, better extinction recall. Moreover, lower AMYG-HPC static RS-FC following extinction learning mediated the link between THC administration and extinction recall. Post-extinction RS-FC patterns may reflect sustained effects of THC on fear-extinction circuitry even in the absence of an overt task, and/or effects of ongoing processes that serve to strengthen the neural connections supporting the consolidation of the memory and better extinction recall.

【 授权许可】

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