Neuropsychiatric Sequelae in Adolescents With Acute Synthetic Cannabinoid Toxicity.

Background And Objectives: Adolescents represent the largest age group that presents to emergency departments (ED) for synthetic cannabinoid (SC) toxicity; however, the neurotoxic effects of acute SC exposures in this group are understudied. Our aim was to characterize the neuropsychiatric presentation of adolescents with SC-related exposure in the ED compared with those with traditional cannabis exposure.

Methods: A multicenter registry of clinical information prospectively collected by medical toxicologists (Toxicology Investigators Consortium Case Registry) was reviewed for adolescents presenting to the ED after SC or cannabis exposure from 2010 through 2018.

Epigenetic basis of opiate suppression of Bdnf gene expression in the ventral tegmental area.

Brain-derived neurotrophic factor (BDNF) has a crucial role in modulating neural and behavioral plasticity to drugs of abuse. We found a persistent downregulation of exon-specific Bdnf expression in the ventral tegmental area (VTA) in response to chronic opiate exposure, which was mediated by specific epigenetic modifications at the corresponding Bdnf gene promoters. Exposure to chronic morphine increased stalling of RNA polymerase II at these Bdnf promoters in VTA and altered permissive and repressive histone modifications and occupancy of their regulatory proteins at the specific promoters.

Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks.

The ability to map the functional connectivity of discrete cell types in the intact mammalian brain during behavior is crucial for advancing our understanding of brain function in normal and disease states. We combined designer receptor exclusively activated by designer drug (DREADD) technology and behavioral imaging with μPET and [18F]fluorodeoxyglucose (FDG) to generate whole-brain metabolic maps of cell-specific functional circuits during the awake, freely moving state. We have termed this approach DREADD-assisted metabolic mapping (DREAMM) and documented its ability in rats to map whole-brain functional anatomy.

Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression.

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects.