Modulation of GBC and DMN connectivity by the alcohol relapse phenotype
depressive disorder, retrosplenial, auditory and hippocampal
CORTEX
While such psilocybin-specific therapeutic mechanisms are increasingly investigated for major depressive disorder, studies focusing on specific mechanistic pathways in AUD are lacking. Investigating psilocybin-induced neural effects in a translational AUD model, our study demonstrates rather comparable effects of psilocybin on FC in alcohol-dependent and control animals, with no treatment-by-subgroup interaction effects in the categorical approach. This is in line with previous investigations using microarray gene chips, exhibiting a limited number of significantly differentially expressed genes in the ADE model compared to control animals [Firstly, ADE animals with higher relapse intensity experienced weaker effects of psilocybin on GBC, mostly affecting parietal auditory, visual areas and nucleus accumbens. Such diminished psilocybin responsivity can potentially be attributed to a disease-specific anaplasticity phenomenon. The anaplasticity concept is characterized by the loss of neuronal and molecular plasticity following external stimulation in the addicted brain, specifically within the nucleus accumbens [Secondly, we show that psilocybin-induced hypoconnectivity of the DMN was broadly and significantly correlated with the relapse intensity of alcohol-dependent rats. We could demonstrate that increased relapse intensity correlates with a diminished effect of psilocybin dose on DMN hypoconnectivity, especially of the mPFC, but also of retrosplenial, auditory and hippocampal areas. Excessive alcohol intake has profound structural and functional impact on the brain. Recent MRI experiments in various rodent models of AUD found altered activity and connectivity patterns in numerous brain regions but particularly in the prefrontal cortex [Considering that psilocybin-induced changes of DMN-network integrity correlate with the psychedelic experience [