The single-cell opioid responses in the context of HIV (SCORCH) consortium

Abstract

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

Fig. 1. Neural circuitry underlying substance use disorders and addiction.

Brain regions: BLA basolateral amygdala, CeA central amygdala, BNST bed nucleus of the stria terminalis, NAc nucleus accumbens, VTA ventral tegmental area, SNc substantia nigra. Neurotransmitters: NE norepinephrine, CRF corticotropin-releasing factor, DA dopamine.

Fig. 2. The Single-cell opioid responses in the context of HIV (SCORCH) consortium.

A The SCORCH consortium will characterize the effects of SUD and HIV in the brain by elucidating the diversity of cell types (1) and cell type-specific molecular adaptations (2) via single-cell genomics in multiple brain regions of humans, non-human primates, and rodents. Key results will be validated through orthogonal approaches, including spatial transcriptomic profiling of brain tissues and genetic perturbation studies in human organoids and rodent models. (3). Data resources from these experiments will be publicly available through the SCORCH Data Center (4). B Data will be collected across 12 projects using brain tissue from humans, non-human primates, and rodent models. C Collectively, SCORCH researchers will investigate >15 brain regions relevant to SUD and HIV.