Transcriptional Profile of Exercise-Induced Protection Against Relapse to Cocaine Seeking in a Rat Model

Towers, Eleanor Blair; Shapiro, Daniel; Abel, Jean M.; Bakhti-Suroosh, Anousheh; Kupkova, Kristyna; Auble, David T.; Grant, Patrick A.; Lynch, Wendy J.

doi:10.1016/j.bpsgos.2023.01.007

Cited by 3 publications

(2 citation statements)

References 88 publications

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“…Similarly, SLC9A3R1, a regulator of vesicle-mediated transport, also was down-regulated. These proteins have been previously highlighted in CUD research (65)(66)(67)(68)(69). The observed modulation in membrane Fig.…”

Section: Discussionmentioning

confidence: 65%

“…A detailed exploration of the transporter activity cluster revealed several proteins with known associations to cocaine withdrawal, including GRIN2A (glutamate receptor ionotropic, NMDA 2A), ANK2 (ankyrin-2), and cyclin-dependent kinase 5 (CDK5) (Fig. 5E) ( 65 – 68 ). The cluster delineating the regulation of transport in down-regulated membrane proteins during withdrawal also offered corroborative insights.…”

Section: Resultsmentioning

confidence: 99%

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Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens

Mews,

Sosnick,

Gurung

et al. 2024

Sci. Signal.

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Cocaine use disorder (CUD) is a chronic neuropsychiatric condition that results from enduring cellular and molecular adaptations. Among substance use disorders, CUD is notable for its rising prevalence and the lack of approved pharmacotherapies. The nucleus accumbens (NAc), a region that is integral to the brain’s reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors that are intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook a proteomic analysis that spanned membrane, cytosolic, nuclear, and chromatin compartments of the NAc in a mouse model. The results unveiled immediate and sustained proteomic modifications after cocaine exposure and during prolonged withdrawal. We identified congruent protein regulatory patterns during initial cocaine exposure and reexposure after withdrawal, which contrasted with distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicated adaptive and long-lasting molecular responses prompted by cocaine withdrawal. In addition, we identified potential protein translocation events between soluble-nuclear and chromatin-bound compartments, thus providing insight into intracellular protein dynamics after cocaine exposure. Together, our findings illuminate the intricate proteomic landscape that is altered in the NAc by cocaine use and provide a dataset for future research toward potential therapeutics.

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Section: Discussionmentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens

Mews,

Sosnick,

Gurung

et al. 2024

Sci. Signal.

View full text Add to dashboard Cite

show abstract

Exploring the progression of drug dependence in a methamphetamine self-administration rat model through targeted and non-targeted metabolomics analyses

Song,

Kim,

Jang

et al. 2024

Sci Rep

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Persistent neurochemical and biological disturbances resulting from repeated cycles of drug reward, withdrawal, and relapse contribute to drug dependence. Methamphetamine (MA) is a psychostimulant with substantial abuse potential and neurotoxic effects, primarily affecting monoamine neurotransmitter systems in the brain. In this study, we aimed to explore the progression of drug dependence in rat models of MA self-administration, extinction, and reinstatement through targeted and non-targeted metabolomics analyses. Metabolic profiles were examined in rat plasma during the following phases: after 16 days of MA self-administration (Group M); after 16 days of self-administration followed by 14 days of extinction (Group MS); and after self-administration and extinction followed by a reinstatement injection of MA (Group MSM). Each group of MA self-administration, extinction, and reinstatement induces distinct changes in the metabolic pathways, particularly those related to the TCA cycle, arginine and proline metabolism, and arginine biosynthesis. Additionally, the downregulation of glycerophospholipids and sphingomyelins in Group MSM suggests their potential role in MA reinstatement. These alterations may signify the progressive deterioration of these metabolic pathways, possibly contributing to drug dependence following repeated cycles of drug reward, withdrawal, and relapse. These results provide valuable insights into the metabolic changes associated with MA use at various stages, potentially facilitating the discovery of early diagnostic biomarkers and therapeutic targets for MA use disorders. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-73247-5.

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Epigenetic and Genetic Profiling of Comorbidity Patterns among Substance Dependence Diagnoses

Pathak,

Pietrzak,

Lacobelle

et al. 2024

Preprint

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Objective: This study investigated the genetic and epigenetic mechanisms underlying the comorbidity patterns of five substance dependence diagnoses (SDs; alcohol, AD; cannabis, CaD; cocaine, CoD; opioid, OD; tobacco, TD). Methods: A latent class analysis (LCA) was performed on 31,197 individuals (average age 42+-11 years; 49% females) from six cohorts to identify comorbid DSM-IV SD patterns. In subsets of this sample, we tested SD-latent classes with respect to polygenic burden of psychiatric and behavioral traits and epigenome-wide changes in three population groups. Results: An LCA identified four latent classes related to SD comorbidities: AD+TD, CoD+TD, AD+CoD+OD+TD (i.e., polysubstance use, PSU), and TD. In the epigenome-wide association analysis, SPATA4 cg02833127 was associated with CoD+TD, AD+TD, and PSU latent classes. AD+TD latent class was also associated with CpG sites located on ARID1B, NOTCH1, SERTAD4, and SIN3B, while additional epigenome-wide significant associations with CoD+TD latent class were observed in ANO6 and MOV10 genes. PSU-latent class was also associated with a differentially methylated region in LDB1. We also observed shared polygenic score (PGS) associations for PSU, AD+TD, and CoD+TD latent classes (i.e., attention-deficit hyperactivity disorder, anxiety, educational attainment, and schizophrenia PGS). In contrast, TD-latent class was exclusively associated with posttraumatic stress disorder-PGS. Other specific associations were observed for PSU-latent class (subjective wellbeing-PGS and neuroticism-PGS) and AD+TD-latent class (bipolar disorder-PGS). Conclusions: We identified shared and unique genetic and epigenetic mechanisms underlying SD comorbidity patterns. These findings highlight the importance of modeling the co-occurrence of SD diagnoses when investigating the molecular basis of addiction-related traits.

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Transcriptional Profile of Exercise-Induced Protection Against Relapse to Cocaine Seeking in a Rat Model

Cited by 3 publications

References 88 publications

Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens

Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens

Exploring the progression of drug dependence in a methamphetamine self-administration rat model through targeted and non-targeted metabolomics analyses

Epigenetic and Genetic Profiling of Comorbidity Patterns among Substance Dependence Diagnoses

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