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

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.

Impulsivity and Drug Addiction: A Neurobiological Perspective

2012 ◽  
Author(s):  
Trevor Robbins
Keyword(s):  
Drug Addiction ◽  
Conceptual Analysis ◽  
Animal Studies ◽  
Reaction Time Task ◽  
Compulsive Behavior ◽  
Self Administration ◽  
Detailed Characterization ◽  
Cocaine Seeking ◽  
Serial Reaction

A conceptual analysis of the impulsivity construct in behavioral and neurobiological terms is followed by an analysis of its causal role in certain forms of drug addiction in both human and animal studies. The main focus of this chapter is on a rat model of impulsivity based on premature responding in the five-choice serial reaction time task and a more detailed characterization of this phenotype in neurobehavioral, neurochemical, and genetic terms. Evidence is surveyed that high impulsivity on this task is associated with the escalation subsequently of cocaine self-administration behavior and also with a tendency toward compulsive cocaine seeking. Novelty reactivity, by contrast, is associated with the enhanced acquisition of self-administration, but not with the escalation of intravenous self-administration of cocaine or the development of compulsive behavior associated with cocaine seeking. These results indicate that the vulnerability to stimulant addiction may depend on different factors, as expressed through distinct presumed endophenotypes. These observations help us further to dissociate various aspects of the impulsivity construct in neural as well as behavioral terms.

scholarly journals Effects of adolescent caffeine consumption on cocaine self-administration and reinstatement of cocaine seeking

2018 ◽  
Vol 33 (1) ◽  
pp. 132-144
Author(s):  
Tracey A Larson ◽  
Casey E O’Neill ◽  
Michaela P Palumbo ◽  
Ryan K Bachtell
Keyword(s):  
Dose Response ◽  
Extinction Training ◽  
Schedules Of Reinforcement ◽  
Sprague Dawley ◽  
Self Administration ◽  
Caffeine Consumption ◽  
Adult Rats ◽  
Sprague Dawley Rats ◽  
Cocaine Seeking ◽  
Administration Procedure

Background: Caffeine consumption by children and adolescents has risen dramatically in recent years, yet the lasting effects of caffeine consumption during adolescence remain poorly understood. Aim: These experiments explore the effects of adolescent caffeine consumption on cocaine self-administration and seeking using a rodent model. Methods: Sprague-Dawley rats consumed caffeine for 28 days during the adolescent period. Following the caffeine consumption period, the caffeine solution was replaced with water for the remainder of the experiment. Age-matched control rats received water for the duration of the study. Behavioral testing in a cocaine self-administration procedure occurred during adulthood (postnatal days 62–82) to evaluate how adolescent caffeine exposure influenced the reinforcing properties of cocaine. Cocaine seeking was also tested during extinction training and reinstatement tests following cocaine self-administration. Results: Adolescent caffeine consumption increased the acquisition of cocaine self-administration and increased performance on different schedules of reinforcement. Consumption of caffeine in adult rats did not produce similar enhancements in cocaine self-administration. Adolescent caffeine consumption also produced an upward shift in the U-shaped dose response curve on cocaine self-administration maintained on a within-session dose-response procedure. Adolescent caffeine consumption had no effect on cocaine seeking during extinction training or reinstatement of cocaine seeking by cues or cocaine. Conclusions: These findings suggest that caffeine consumption during adolescence may enhance the reinforcing properties of cocaine, leading to enhanced acquisition that may contribute to increased addiction vulnerability.

scholarly journals Maternal Diet Influences the Reinstatement of Cocaine-Seeking Behavior and the Expression of Melanocortin-4 Receptors in Female Offspring of Rats

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1462
Author(s):  
Dawid Gawliński ◽  
Kinga Gawlińska ◽  
Małgorzata Frankowska ◽  
Małgorzata Filip
Keyword(s):  
Maternal Diet ◽  
Dorsal Striatum ◽  
Brain Structures ◽  
Female Offspring ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Pregnancy And Lactation ◽  
The Impact ◽  
Cocaine Reward

Recent studies have emphasized the role of the maternal diet in the development of mental disorders in offspring. Substance use disorder is a major global health and economic burden. Therefore, the search for predisposing factors for the development of this disease can contribute to reducing the health and social damage associated with addiction. In this study, we focused on the impact of the maternal diet on changes in melanocortin-4 (MC-4) receptors as well as on behavioral changes related to cocaine addiction. Rat dams consumed a high-fat diet (HFD), high-sugar diet (HSD, rich in sucrose), or mixed diet (MD) during pregnancy and lactation. Using an intravenous cocaine self-administration model, the susceptibility of female offspring to cocaine reward and cocaine-seeking propensities was evaluated. In addition, the level of MC-4 receptors in the rat brain structures related to cocaine reward and relapse was assessed. Modified maternal diets did not affect cocaine self-administration in offspring. However, the maternal HSD enhanced cocaine-seeking behavior in female offspring. In addition, we observed that the maternal HSD and MD led to increased expression of MC-4 receptors in the nucleus accumbens, while increased MC-4 receptor levels in the dorsal striatum were observed after exposure to the maternal HSD and HFD. Taken together, it can be concluded that a maternal HSD is an important factor that triggers cocaine-seeking behavior in female offspring and the expression of MC-4 receptors.

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 Fos Protein Expression and Cocaine-Seeking Behavior in Rats after Exposure to a Cocaine Self-Administration Environment

2000 ◽  
Vol 20 (2) ◽  
pp. 798-805 ◽  
Author(s):  
Janet L. Neisewander ◽  
David A. Baker ◽  
Rita A. Fuchs ◽  
Ly T. L. Tran-Nguyen ◽  
Art Palmer ◽  
...  
Keyword(s):  
Protein Expression ◽  
Self Administration ◽  
Fos Protein ◽  
Cocaine Seeking ◽  
Seeking Behavior

scholarly journals Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

2016 ◽  
Vol 113 (20) ◽  
pp. E2861-E2870 ◽  
Author(s):  
Shelly B. Flagel ◽  
Sraboni Chaudhury ◽  
Maria Waselus ◽  
Rebeca Kelly ◽  
Salima Sewani ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Protective Factor ◽  
Dopamine D2 Receptor ◽  
Genetic Difference ◽  
Epigenetic Modifications ◽  
Mrna Levels ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
The Core ◽  
Cocaine Seeking

This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with “temperament,” including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor.

scholarly journals Extinction Training after Cocaine Self-Administration Induces Glutamatergic Plasticity to Inhibit Cocaine Seeking

2010 ◽  
Vol 30 (23) ◽  
pp. 7984-7992 ◽  
Author(s):  
L. A. Knackstedt ◽  
K. Moussawi ◽  
R. Lalumiere ◽  
M. Schwendt ◽  
M. Klugmann ◽  
...  
Keyword(s):  
Extinction Training ◽  
Self Administration ◽  
Cocaine Seeking

scholarly journals Inactivation of NMDA Receptors in the Ventral Tegmental Area during Cocaine Self-Administration Prevents GluA1 Upregulation but with Paradoxical Increases in Cocaine-Seeking Behavior

2017 ◽  
Vol 38 (3) ◽  
pp. 575-585 ◽  
Author(s):  
Daniel Guzman ◽  
Maria B. Carreira ◽  
Allyson K. Friedman ◽  
Megumi Adachi ◽  
Rachael L. Neve ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Ventral Tegmental Area ◽  
Self Administration ◽  
Cocaine Seeking ◽  
Seeking Behavior ◽  
Ventral Tegmental

scholarly journals mGlu5 Receptors and Relapse to Cocaine-Seeking: The Role of Receptor Trafficking in Postrelapse Extinction Learning Deficits

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lori A. Knackstedt ◽  
Marek Schwendt
Keyword(s):  
Relapse Prevention ◽  
Operant Chamber ◽  
Treatment Strategies ◽  
Surface Expression ◽  
Self Administration ◽  
Extinction Learning ◽  
Learning Deficits ◽  
Cocaine Seeking ◽  
Mglu5 Receptors

We have previously demonstrated that MTEP, an allosteric antagonist of mGlu5, infused into the nucleus accumbens attenuates relapse after abstinence from cocaine self-administration. MTEP infused into the dorsolateral striatum (dlSTR) does not alter relapse but has long-lasting effects on subsequent extinction learning. Here we tested whether systemic MTEP would prevent relapse after abstinence or alter extinction learning. We also investigated the mechanism of action by which intra-dlSTR MTEP on test day alters extinction on subsequent days. Animals self-administered cocaine for 12 days followed by abstinence for 20-21 days. MTEP (0.5–5 mg/kg IP) was administered prior to placement into the operant chamber for a context-primed relapse test. A separate group of animals received intra-dlSTR MTEP prior to the relapse test and were sacrificed day later. Systemic administration of MTEP attenuated abstinent-relapse without significantly affecting extinction learning. Surface biotinylation analysis of protein expression in the dlSTR revealed that, in cocaine animals, intra-dlSTR MTEP administration decreased mGlu5 surface expression and prevented changes in Arc and GluA1/GluA2 observed in their vehicle counterparts. Thus, blockade of mGlu5 receptors may be utilized in future treatment strategies for relapse prevention in humans, although the effects of chronic blockade on extinction learning should be further evaluated.

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