nnCingulate circuits are associated with escalation of heroin use and naloxone-induced increases in heroin self-administration

Abstract The current opioid epidemic necessitates a better understanding of human addiction neurobiology to develop efficacious treatment approaches. Here, we perform genome-wide assessment of chromatin accessibility of the human striatum in heroin users and matched controls. Our study reveals distinct neuronal and non-neuronal epigenetic signatures, and identifies a locus in the proximity of the gene encoding tyrosine kinase FYN as the most affected region in neurons. FYN expression, kinase activity and the phosphorylation of its target Tau are increased by heroin use in the post-mortem human striatum, as well as in rats trained to self-administer heroin and primary striatal neurons treated with chronic morphine in vitro. Pharmacological or genetic manipulation of FYN activity significantly attenuates heroin self-administration and responding for drug-paired cues in rodents. Our findings suggest that striatal FYN is an important driver of heroin-related neurodegenerative-like pathology and drug-taking behavior, making FYN a promising therapeutic target for heroin use disorder.

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Female rats self-administer heroin by vapor inhalation

10.1101/2020.03.30.016725 ◽

2020 ◽

Cited By ~ 3

Author(s):

Arnold Gutierrez ◽

Jacques D. Nguyen ◽

Kevin M. Creehan ◽

Michael A. Taffe

Keyword(s):

The United States ◽

Route Of Administration ◽

Female Rats ◽

Initial Increase ◽

Prescription Opioids ◽

Self Administration ◽

Heroin Use ◽

Male And Female Rats ◽

Opioid Drugs ◽

Withdrawal Signs

AbstractOver the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24-48 hours after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin or other opioids.

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Individual vulnerability to stress is associated with increased demand for intravenous heroin self-administration in rats

10.1101/627471 ◽

2019 ◽

Author(s):

Nathaniel P. Stafford ◽

Theodore N. Kazan ◽

Colleen M. Donovan ◽

Erin E. Hart ◽

Robert C. Drugan ◽

...

Keyword(s):

Stress Reactivity ◽

Biological Response ◽

Male Rats ◽

Opioid Use ◽

Self Administration ◽

Heroin Use ◽

Individual Vulnerability ◽

Before And After ◽

Individual Demand ◽

Vulnerability To Stress

AbstractOpioid use is a widespread epidemic, and traumatic stress exposure is a critical risk factor in opioid use and relapse. There is a significant gap in our understanding of how stress contributes to heroin use, and there are limited studies investigating individual differences underlying stress reactivity and subsequent stress-induced heroin self-administration. We hypothesized that greater individual vulnerability to stress would predict higher demand for heroin self-administration in a within-subjects rodent model of stress and heroin use comorbidity. Male rats were exposed to inescapable intermittent swim stress and individual biological (corticosterone) or behavioral (open field, social exploration, and forced swim tests) measures were assessed before and after the stress episode. Individual demand for self-administered heroin (0.05 mg/kg/infusion; 12-hour sessions) was assessed using a behavioral economics approach followed by extinction and reinstatement tests triggered by stress re-exposure, non-contingent cue presentations, and yohimbine (0, 1.0, or 2.5 mg/kg). We found that behavioral, biological, and a combination of behavioral and biological markers sampled prior and after the stress episode that occurred weeks before the access to heroin selfadministration predicted the magnitude of individual demand for heroin. Non-contingent presentation of cues, that were previously associated with heroin, reinstated heroin seeking in extinction. For the first time, we show that individual biological response to an ecologically relevant stressor in combination with associated behavioral markers can be used to predict subsequent economic demand for heroin.

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Self-administration of Cyclofem acceptable to some women in Brazil

Reproductive Health Matters ◽

10.1016/s0968-8080(99)90136-2 ◽

1999 ◽

Vol 7 (13) ◽

pp. 158

Keyword(s):

Self Administration

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Collection of Ego-Centered Network Data with Computer-Assisted Interviews

Methodology ◽

10.1027/1614-2241.2.1.7 ◽

2006 ◽

Vol 2 (1) ◽

pp. 7-15 ◽

Cited By ~ 10

Author(s):

Joachim Gerich ◽

Roland Lehner

Keyword(s):

Survey Methods ◽

A Priori ◽

Dynamic Structure ◽

Computer Assisted ◽

Network Data ◽

Great Effort ◽

Self Administration ◽

Face To Face ◽

Full Network

Although ego-centered network data provide information that is limited in various ways as compared with full network data, an ego-centered design can be used without the need for a priori and researcher-defined network borders. Moreover, ego-centered network data can be obtained with traditional survey methods. However, due to the dynamic structure of the questionnaires involved, a great effort is required on the part of either respondents (with self-administration) or interviewers (with face-to-face interviews). As an alternative, we will show the advantages of using CASI (computer-assisted self-administered interview) methods for the collection of ego-centered network data as applied in a study on the role of social networks in substance use among college students.

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