scholarly journals Sex and heredity are determinants of drug intake in a novel model of rat oral oxycodone self‐administration

2021 ◽  
Author(s):  
Burt M. Sharp ◽  
Xinyu Fan ◽  
Eva E. Redei ◽  
Mulligan K. Megan ◽  
Hao Chen
Keyword(s):  
Drug Intake ◽  
Self Administration ◽  
Novel Model

scholarly journals Fentanyl vapor self-administration model in mice to study opioid addiction

2020 ◽  
Vol 6 (32) ◽  
pp. eabc0413 ◽  
Author(s):  
K. Moussawi ◽  
M. M. Ortiz ◽  
S. C. Gantz ◽  
B. J. Tunstall ◽  
R. C. N. Marchette ◽  
...  
Keyword(s):  
Mouse Model ◽  
Opioid Addiction ◽  
Dopamine Neurons ◽  
Drug Intake ◽  
Self Administration ◽  
Protracted Abstinence ◽  
Electrophysiological Recordings ◽  
Lower Amplitude ◽  
The Many ◽  
Intravenous Catheterization

Intravenous drug self-administration is considered the “gold standard” model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABAB receptor–dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

scholarly journals Drug Intake is Sufficient, but Conditioning is not Necessary for the Emergence of Compulsive Cocaine Seeking After Extended Self-Administration

2012 ◽  
Vol 37 (7) ◽  
pp. 1612-1619 ◽  
Author(s):  
Sietse Jonkman ◽  
Yann Pelloux ◽  
Barry J Everitt
Keyword(s):  
Drug Intake ◽  
Self Administration ◽  
Extended Self ◽  
Cocaine Seeking

P6.d.004 Depressive-like behaviour and aripiprazole increase the drug intake in iv self-administration model in rats

2009 ◽  
Vol 19 ◽  
pp. S659-S660
Author(s):  
J. Kucerova ◽  
J. Pistovcakova ◽  
D. Vrskova ◽  
M. Nemecek ◽  
A. Sulcova
Keyword(s):  
Drug Intake ◽  
Self Administration

scholarly journals Parsing the addiction phenomenon: Self-administration procedures modeling enhanced motivation for drug and escalation of drug intake

2008 ◽  
Vol 5 (4) ◽  
pp. 217-226 ◽  
Author(s):  
Erik B. Oleson ◽  
David C.S. Roberts
Keyword(s):  
Drug Intake ◽  
Self Administration

scholarly journals Drug-associated cues and drug dosage contribute to increased opioid seeking after abstinence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Tresa Zanda ◽  
Gabriele Floris ◽  
Stephanie E. Sillivan
Keyword(s):  
Drug Dosage ◽  
Opioid Use Disorder ◽  
Drug Intake ◽  
Opioid Use ◽  
Self Administration ◽  
Drug Seeking ◽  
Drug Cues ◽  
Rehabilitation Programs ◽  
Key Factor ◽  
Seeking Behavior

AbstractPatients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence.

scholarly journals The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse

2020 ◽  
Author(s):  
Dhaval D. Joshi ◽  
Mickaël Puaud ◽  
Maxime Fouyssac ◽  
Aude Belin-Rauscent ◽  
Barry Everitt ◽  
...  
Keyword(s):  
Insular Cortex ◽  
Drug Intake ◽  
Inhibitory Influence ◽  
Loss Of Control ◽  
Self Administration ◽  
Anterior Insular Cortex ◽  
State Dependent ◽  
Extended Access ◽  
History Of

AbstractThe anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug-related behaviours is complex since in rats exposed to extended access to cocaine self-administration, the AIC was shown to exert a state-dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. Thus, we investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC, induced both prior to or after long-term exposure to extended access heroin self-administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham-surgeries, pre-exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.

scholarly journals Tropisetron Facilitates Footshock Suppression of Compulsive Cocaine Seeking

2019 ◽  
Vol 22 (9) ◽  
pp. 574-584
Author(s):  
Yue-Qing Zhou ◽  
Lan-Yuan Zhang ◽  
Zhi-Peng Yu ◽  
Xiao-Qin Zhang ◽  
Jie Shi ◽  
...  
Keyword(s):  
Training Session ◽  
Progressive Ratio ◽  
Drug Intake ◽  
Ratio Schedule ◽  
Progressive Ratio Schedule ◽  
Dosing Regimen ◽  
Self Administration ◽  
Drug Seeking ◽  
Cocaine Seeking ◽  
Long Access

AbstractBackgroundThe hallmark characteristics of the murine model of drug addiction include the escalation of cocaine consumption and compulsive punishment-resistant drug seeking. In this study, we evaluated the motivation for drug seeking in cocaine self-administering rats exposed to an escalated dosing regimen that endeavored to mimic the characteristic of escalating drug intake in human addicts. Tropisetron is a 5-HT3 receptor antagonist and α7-nicotinic receptor partial agonist. Utilizing rats trained on the escalated-dosing regimen, we examined the effects of tropisetron on control over compulsive drug-seeking behavior that was defined as footshock-resistant lever pressing.MethodsRats were trained to self-administer cocaine with incremental-infusion doses (from 0.6 to 2.4 mg/kg/infusion) across training sessions (3 h/session) or with a long-access paradigm (i.e., 0.6 mg/kg/infusion, 6 h/d training session). The drug-seeking motivations of 2 groups were estimated by the patterns of drug intake and progressive-ratio schedule. The compulsivity for drug seeking of the group with an escalated dose was further evaluated using the footshock-associated seeking-taking chain task.ResultsThe rats trained on the dose-escalated protocol achieved the same levels of motivated drug seeking as those subjected to a long-access paradigm, as indicated by cocaine intake per training session and breakpoints on a progressive ratio schedule. Tropisetron attenuated compulsive behavior of rats when pressing of the seeking lever potentially led to footshock. Intriguingly, tropisetron did not change the motivation to seek cocaine when footshock was absent. Tropisetron had no effect on locomotor activities or saccharin self-administration.ConclusionsThese results demonstrate that tropisetron restored control over compulsive cocaine seeking, and they indicate that 5-HT3/α7-nicotinic receptors may be potential therapeutic targets for relieving compulsive drug seeking.

Opioid Self-administration in the Nerve-injured Rat

2007 ◽  
Vol 106 (2) ◽  
pp. 312-322 ◽  
Author(s):  
Thomas J. Martin ◽  
Susy A. Kim ◽  
Nancy L. Buechler ◽  
Frank Porreca ◽  
James C. Eisenach
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Intrathecal Administration ◽  
Spinal Nerve ◽  
Spinal Nerve Ligation ◽  
Drug Intake ◽  
Spontaneous Pain ◽  
Self Administration ◽  
Mechanical Hypersensitivity ◽  
Opioid Sparing

Background Neuropathic pain is associated with several sensory abnormalities, including allodynia as well as spontaneous pain. Opioid intake in neuropathic pain patients is motivated by alleviation of both pain and allodynia. However, laboratory animal studies rely almost exclusively on reflexive withdrawal measures of allodynia. The authors examined the pharmacology of self-regulated intake of opioids in rats with or without nerve injury and compared the rate of drug intake to reversal of allodynia. Methods Rats were implanted with intravenous catheters, and the L5 and L6 spinal nerves were ligated in half of these animals. Rats were then trained to self-administer a commonly abused opioid (heroin) and commonly prescribed opioids (morphine, fentanyl, hydromorphone, and methadone). In addition, rats trained to self-administer heroin were given either clonidine or adenosine spinally before self-administration sessions to assess opioid-sparing effects. Results Nerve injury significantly decreased the reinforcing effects of low doses of opioids, and only doses of each opioid that reduced mechanical hypersensitivity maintained self-administration after spinal nerve ligation. The rate of drug consumption was correlated with the duration of the antiallodynic effect for each dose of opioid. Intrathecal administration of clonidine or adenosine reversed mechanical hypersensitivity, but only clonidine reduced heroin self-administration in rats with spinal nerve ligation. Conclusion Opioid self-administration is significantly altered by nerve injury, with rate of drug intake being correlated with reversal of allodynia. Intrathecal clonidine, but not adenosine, produces opioid-sparing effects in self-administering rats. The neurobiologic mechanisms that regulate opioid consumption in rats therefore seem to be altered after nerve injury.

scholarly journals Vaping nicotine-containing electronic cigarettes produces addiction-like behaviors and cardiopulmonary abnormalities in rats

2019 ◽  
Author(s):  
Lauren C. Smith ◽  
Marsida Kallupi ◽  
Lani Tieu ◽  
Abigail Jaquish ◽  
Jamie Barr ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Nicotine Dependence ◽  
Healthcare Professionals ◽  
Electronic Cigarettes ◽  
Pulmonary Complications ◽  
Electronic Cigarette ◽  
Self Administration ◽  
Novel Model ◽  
Harmful Effects

AbstractThe debate about electronic cigarettes has divided healthcare professionals, policymakers, and communities. Central points of disagreement are whether vaping electronic cigarettes are addictive and whether they produce major pulmonary complications. We developed a novel model of nicotine vapor self-administration in rats and found that rats voluntarily exposed themselves to nicotine vapor to the point of reaching blood nicotine levels that are similar to humans, exhibiting both addiction-like behaviors and cardiopulmonary abnormalities. The smoking cessation drug varenicline decreased electronic cigarette self-administration. These findings confirm the addictive properties and harmful effects of nicotine vapor and identify a potential medication for the treatment of electronic cigarette addiction.One Sentence SummaryVaping nicotine-containing electronic cigarettes produces cardiopulmonary abnormalities, nicotine dependence and addiction-like behaviors, which are reduced by the smoking cessation drug varenicline.

scholarly journals An optimized procedure for robust volitional drug intake in mice

2019 ◽  
Author(s):  
Alberto J. López ◽  
Amy R. Johnson ◽  
Ansley J. Kunnath ◽  
Jennifer E. Zachry ◽  
Kimberly C. Thibeault ◽  
...  
Keyword(s):  
Substance Use ◽  
Mouse Models ◽  
Substance Use Disorder ◽  
Fixed Ratio ◽  
Drug Intake ◽  
Sex Bias ◽  
Variable Ratio ◽  
Inclusion Criteria ◽  
Self Administration ◽  
Schedule Of Reinforcement

Substance use disorder is a behavioral disorder characterized by volitional drug consumption, compulsive behavior, drug seeking, and relapse. Mouse models of substance use disorder allow for the use of molecular, genetic, and circuit level tools, which provide enormous potential for defining the underlying mechanisms of this disorder. However, the relevance of results depends entirely on the validity of the mouse models used. Self-administration models have long been considered the gold standard of preclinical addiction models, as they allow for volitional drug use, this providing strong face validity. In a series of experiments, we show that traditional mouse models of self-administration, where behavior is maintained on a fixed-ratio one schedule of reinforcement, show similar levels of responding in the presence and absence of drug delivery - demonstrating that it is impossible to determine when intake is and is not volitional. Further, when assessing inclusion criteria, we find a sex-bias in exclusion criteria where females that acquired food self-administration were eliminated when traditional criteria were applied. To address these issues, we have developed a novel mouse self-administration procedure where animals do not need to be pre-trained on food and behavior is maintained on a variable ratio schedule of reinforcement. This procedure increases rates of reinforcement behavior, increases levels of drug intake, and eliminates sex bias in inclusion criteria. Together, these data highlight a major issue with fixed-ratio models in mice that complicates subsequent analysis and provide a simple and novel approach to minimize these confounds with escalating variable-ratio schedules of reinforcement.

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