Dataset Information

Development of a novel alcohol and nicotine concurrent access (ANCA) self-administration procedure in baboons.

ABSTRACT:

Background

Self-administration of either alcohol or nicotine under single-access conditions has been studied extensively in laboratory animals. Relatively few studies have examined the co-use of these substances, even though alcohol and nicotine use and abuse commonly co-occur in humans. The objectives of this study were to develop a baboon model of concurrent alcohol and nicotine self-administration, and examine effects of varenicline on alcohol and nicotine co-use.

Methods

In Experiment 1, five male baboons were trained to self-administer drinks of alcohol (4% w/v) and injections of nicotine (0.032-0.1?mg/kg) under single-access and then concurrent-access conditions, and intake of alcohol (g/kg) and nicotine (mg/kg) was compared under single- and concurrent-access conditions. In Experiment 2, three male baboons self-administered drinks of alcohol (4% w/v) and injections of nicotine (0.056?mg/kg) under concurrent-access conditions. Pretreatment with varenicline (0.32-1.0?mg/kg, s.c.) or an equal volume of its vehicle before concurrent-access sessions was repeated for 5 consecutive days.

Results

Self-administration of nicotine and alcohol was successfully established under both single- and concurrent-access conditions that produced reliable levels of voluntary alcohol and nicotine intake. Co-self-administration of both drugs produced levels of intake similar to that produced by each drug alone. Varenicline significantly reduced intake of both alcohol and nicotine when compared to the vehicle condition.

Conclusions

This baboon model provides a valuable tool for further investigation of the behavioral and pharmacological mechanisms involved in co-use of nicotine and alcohol. A single pharmacotherapeutic agent (e.g., varenicline) may be useful in treating nicotine and alcohol co-use.

SUBMITTER: Holtyn AF

PROVIDER: S-EPMC6980761 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Development of a novel alcohol and nicotine concurrent access (ANCA) self-administration procedure in baboons.

Holtyn August F AF Davis Catherine M CM Weerts Elise M EM

Drug and alcohol dependence 20191111

<h4>Background</h4>Self-administration of either alcohol or nicotine under single-access conditions has been studied extensively in laboratory animals. Relatively few studies have examined the co-use of these substances, even though alcohol and nicotine use and abuse commonly co-occur in humans. The objectives of this study were to develop a baboon model of concurrent alcohol and nicotine self-administration, and examine effects of varenicline on alcohol and nicotine co-use.<h4>Methods</h4>In Ex ...[more]

PMID: 31801108

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Project description:BackgroundChronic consumption of most drugs of abuse leads to brain oxidative stress and neuroinflammation, which inhibit the glutamate transporter GLT-1, proposed to perpetuate drug intake. The present study aimed at inhibiting chronic ethanol and nicotine self-administration and relapse by the non-invasive intranasal administration of antioxidant and anti-inflammatory secretome generated by adipose tissue-derived activated mesenchymal stem cells. The anti-addiction mechanism of stem cell secretome is also addressed.MethodsRats bred for their alcohol preference ingested alcohol chronically or were trained to self-administer nicotine. Secretome of human adipose tissue-derived activated mesenchymal stem cells was administered intranasally to animals, both (i) chronically consuming alcohol or nicotine and (ii) during a protracted deprivation before a drug re-access leading to relapse intake.ResultsThe intranasal administration of secretome derived from activated mesenchymal stem cells inhibited chronic self-administration of ethanol or nicotine by 85% and 75%, respectively. Secretome administration further inhibited by 85-90% the relapse "binge" intake that occurs after a protracted drug deprivation followed by a 60-min drug re-access. Secretome administration fully abolished the oxidative stress induced by chronic ethanol or nicotine self-administration, shown by the normalization of the hippocampal oxidized/reduced glutathione ratio, and the neuroinflammation determined by astrocyte and microglial immunofluorescence. Knockdown of the glutamate transporter GLT-1 by the intracerebral administration of an antisense oligonucleotide fully abolished the inhibitory effect of the secretome on ethanol and nicotine intake.ConclusionsThe non-invasive intranasal administration of secretome generated by human adipose tissue-derived activated mesenchymal stem cells markedly inhibits alcohol and nicotine self-administration, an effect mediated by the glutamate GLT-1 transporter. Translational implications are envisioned.

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Dataset Information

Development of a novel alcohol and nicotine concurrent access (ANCA) self-administration procedure in baboons.

Background

Methods

Results

Conclusions

Publications

Development of a novel alcohol and nicotine concurrent access (ANCA) self-administration procedure in baboons.

Similar Datasets

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