A place for the hippocampus in the cocaine addiction circuit: Potential roles for adult hippocampal neurogenesis

Castilla‐Ortega, Estela; Serrano, Antonia; Blanco, Eduardo; Araos, Pedro; Suárez, Juan; Pavón, Francisco Javier; Fonseca, Fernando Rodrı́guez de; Santín, Luis J.

doi:10.1016/j.neubiorev.2016.03.030

Cited by 86 publications

(80 citation statements)

References 191 publications

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“…Evidence is mounting implicating the role of the hippocampus in the pathophysiology of CD. Research suggests that compromised hippocampal neurogenesis/memory formation is a biological mechanism contributing to chronic cocaine use (see Castilla‐Ortega et al for review). One study used transcriptome‐wide RNA‐sequencing (RNA‐seq) and chromatin immunoprecipitation (ChIP) analyses to discover various transcriptional modifications underlying cocaine use in postmortem human hippocampal tissue .…”

Section: Introductionmentioning

confidence: 99%

Cocaine'omics: Genome‐wide and transcriptome‐wide analyses provide biological insight into cocaine use and dependence

Huggett

Stallings

2019

Addiction Biology

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We investigated the genetic and molecular architecture of cocaine dependence (CD) and cocaine use by integrating genome-/transcriptome-wide analyses. To prioritize candidates for follow-up investigation, we also sought to translate gene expression findings across species. Using data from the largest genome-wide association study (GWAS) of CD to date (n = 3176, 74% with CD), we assessed genomic heritability, gene-based associations, and tissue enrichment. We detected a significant singlenucleotide polymorphism heritability of 28% for CD and identified three genes (two loci) underlying this predisposition: the C1qL2 (complement component C1 q like 2), KCTD20 (potassium channel tetramerization domain containing 20), and STK38(serine/threonine kinase 38) genes. Tissue enrichment analyses indicated robust enrichment in numerous brain regions, including the hippocampus. We used postmortem human hippocampal RNA-sequencing data from previous study (n = 15, seven chronic cocaine users) to follow up genome-wide results and to identify differentially expressed genes/transcripts and gene networks underlying cocaine use. Cross-species analyses utilized hippocampal gene expression from a mouse model of cocaine use.Differentially expressed genes/transcripts in humans were enriched for the genes nominally associated with CD via GWAS (P < 0.05) and for differentially expressed genes in the hippocampus of cocaine-exposed mice. We identified KCTD20 as a central component of a hippocampal gene network strongly associated with human cocaine use, and this gene network was conserved in the mouse hippocampus. We outline a framework to map and translate genome-wide findings onto tissue-specific gene expression, which provided biological insight into cocaine use/dependence.

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Section: Introductionmentioning

confidence: 99%

Cocaine'omics: Genome‐wide and transcriptome‐wide analyses provide biological insight into cocaine use and dependence

Huggett

Stallings

2019

Addiction Biology

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“…The mechanisms underlying the causes of drug addiction are not entirely known, but it is thought that the processes of learning and memory are essential and that the hippocampus plays a key role in contextual conditioning and cocaine addiction 1,2 . In fact, addiction has been considered as a type of nonadaptive learning 3 .…”

Section: Introductionmentioning

confidence: 99%

3d Synaptic Organization of the Rat Ca1 and Alterations Induced by Cocaine Self-Administration

Blázquez-Llorca

Miguéns

Montero-Crespo

et al. 2020

Preprint

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The hippocampus plays a key role in contextual conditioning and has been proposed as an important component of the cocaine addiction brain circuit.To gain knowledge about cocaine-induced alterations in this circuit, we used Focused Ion Beam milling/Scanning Electron Microscopy (FIB/SEM) to reveal and quantify the 3D synaptic organization of the stratum radiatum of rat CA1, under normal circumstances and after cocaine-self administration (SA). Most synapses are asymmetric (excitatory), macular-shaped, and in contact with spine heads. After cocaine-SA, the size and complexity of both asymmetric and symmetric (inhibitory) synapses increased but no changes were observed in the synaptic density.This work constitutes the first detailed report on the 3D synaptic organization in the stratum radiatum of the CA1 field of cocaine-SA rats. Our data contribute to the elucidation of the normal and altered synaptic organization of the hippocampus, which is crucial for better understanding the neurobiological mechanisms underlying cocaine addiction.

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“…While the hippocampus is known to be particularly sensitive to stress (e.g., Gould and Tanapat 1999), and involved in several aspects of addiction liability (Castilla-Ortega et al 2016a), including drug-context memory (e.g., Meyers et al 2006) and relapse to drug-seeking (e.g., Vorel et al 2001), the current findings are the first to investigate the relationship between hippocampal cell genesis and Pavlovian conditioned approach responses, specifically as a consequence of adolescent cocaine exposure. Adult hippocampal cell genesis (i.e., cell proliferation and survival; Cameron and McKay 2001) represents one form of hippocampal plasticity that contributes to the brain’s ability to process and respond to challenges (Mandyam and Koob 2012), such as drug exposure (e.g., Noonan et al 2008, 2010) during adolescence.…”

Section: Discussionmentioning

confidence: 89%

“…These phenotype-specific effects are believed to play a role in the bLR/bHR differences in cocaine-induced behavioral sensitization (García-Fuster et al 2010). While the hippocampus has been implicated in addiction-related behaviors (Castilla-Ortega et al 2016a), and in bHR/bLR differences in response to drugs of abuse (García-Fuster et al 2010, 2011; Waselus et al 2013; Flagel et al 2014), the relationship between hippocampal cell fate and the propensity to attribute incentive salience to reward cues (i.e. sign- vs. goal-track) has never been assessed.…”

Section: Introductionmentioning

confidence: 99%

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

et al. 2017

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Rationale Environmental challenges during adolescence, such as drug exposure, can cause enduring behavioral and molecular changes that contribute to life-long maladaptive behaviors, including addiction. Selectively bred high-responder (bHR) and low-responder (bLR) rats represent a unique model for assessing the long-term impact of adolescent environmental manipulations, as they inherently differ on a number of addiction-related traits. bHR rats are considered “addiction-prone”, whereas bLR rats are “addiction-resilient”, at least under baseline conditions. Moreover, relative to bLRs, bHR rats are more likely to attribute incentive motivational value to reward cues, or to “sign-track”. Objectives We utilized bHR and bLR rats to determine whether adolescent cocaine exposure can alter their inborn behavioral and neurobiological profiles, with a specific focus on Pavlovian conditioned approach behavior (i.e. sign- vs. goal-tracking) and hippocampal neurogenesis. Methods bHR and bLR rats were administered cocaine (15 mg/kg) or saline for 7 days during adolescence (postnatal day, PND 33–39) and subsequently tested for Pavlovian conditioned approach behavior in adulthood (PND 62–75), wherein an illuminated lever (conditioned stimulus) was followed by the response-independent delivery of a food pellet (unconditioned stimulus). Behaviors directed towards the lever and the food cup were recorded as sign- and goal-tracking, respectively. Hippocampal cell genesis was evaluated on PND 77 by immunohistochemistry. Results Adolescent cocaine exposure impaired hippocampal cell genesis (proliferation and survival) and enhanced the inherent propensity to goal-track in adult bLR, but not bHR, rats. Conclusions Adolescent cocaine exposure elicits long-lasting changes in stimulus-reward learning and enduring deficits in hippocampal neurogenesis selectively in adult bLR rats.

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A place for the hippocampus in the cocaine addiction circuit: Potential roles for adult hippocampal neurogenesis

Cited by 86 publications

References 191 publications

Cocaine'omics: Genome‐wide and transcriptome‐wide analyses provide biological insight into cocaine use and dependence

Cocaine'omics: Genome‐wide and transcriptome‐wide analyses provide biological insight into cocaine use and dependence

3d Synaptic Organization of the Rat Ca1 and Alterations Induced by Cocaine Self-Administration

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

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