Variability of drug self-administration in rats

Panlilio, Leigh V.; Katz, Jonathan L.; Pickens, Roy W.; Schindler, Charles W.

doi:10.1007/s00213-002-1366-x

Cited by 65 publications

(101 citation statements)

References 55 publications

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“…determined largely by the duration of the effect of each injection (Gerber and Wise, 1989;Panlilio et al, 2003;Tsibulsky and Norman, 1999), but drug-seeking under progressive-ratio schedules is essentially independent of duration of effect (Panlilio and Schindler, 2000; see also Ko et al, 2002). Thus, cross-tolerance to heroin's locomotorsuppressant effects would be expected to increase heroin intake under the FR1 schedule, but it should not alter the reinforcing efficacy of heroin under the progressive-ratio schedule.…”

Section: Discussionmentioning

confidence: 99%

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Panlilio

Solinas

Matthews

et al. 2006

Neuropsychopharmacol

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The hypothesis that prior cannabis exposure increases the likelihood of becoming addicted to other drugs can be evaluated by giving rats a history of tetrahydrocannabinol (THC) exposure, then allowing them to self-administer other drugs. In Experiment 1, THC preexposure did not alter the acquisition of cocaine self-administration or the amount of cocaine taken under a fixed-ratio 1 (FR1) schedule, with one response required for each injection. Under a progressive-ratio schedule, with the response requirement increasing exponentially with each injection, cocaine-seeking was significantly reduced in THC-exposed rats, suggesting that the regimen of THC exposure used in the present study caused cocaine to be devalued as a reinforcer. In contrast, in an earlier study that used the same regimen, a history of THC exposure did not alter the value of heroin as a reinforcer under the progressive-ratio schedule, but it increased heroin self-administration under the FR1 schedule. Experiment 2 examined how this regimen of THC pre-exposure alters the locomotor effects of cocaine and heroin. THC pre-exposure produced cross-tolerance to the motor-depressant effects of heroin; this may explain the shortened post-injection pauses exhibited by THC-exposed rats under FR1 heroin self-administration. When given cocaine, THCexposed rats exhibited normal increases in locomotion, but they avoided the center of the open field, suggesting that this THC preexposure regimen enhances the anxiogenic effects of cocaine. This enhanced anxiogenic effectFwhich was verified in Experiment 3 using another model of anxiety, the light-dark testFmay explain the reduced reinforcing value of cocaine observed in THC-exposed rats in Experiment 1.

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Section: Discussionmentioning

confidence: 99%

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Panlilio

Solinas

Matthews

et al. 2006

Neuropsychopharmacol

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“…General procedure and apparatus were described previously (Scherma et al, 2008;Panlilio et al, 2003). Self-administration sessions were 2 h long and began 7-10 days after catheterization.…”

Section: Drugsmentioning

confidence: 99%

“…Completion of each five-response fixed ratio was treated by the computer as a virtual injection of nicotine, and the rat's virtual nicotine level was calculated continuously based on a clearance half-life of 55 min. The light was only presented when the virtual nicotine level was below 202 mg/kg, the mean level (calculated using the procedure of Panlilio et al, 2003) at which rats self-administered nicotine in a previous study (Mascia et al, 2011). To assess potential interactions between nicotine and clofibrate, half the rats were treated with nicotine (0.4 mg/kg, subcutaneous, 10 min before session) and half with saline before every food self-administration session.…”

Section: Food Self-administration In Ratsmentioning

confidence: 99%

Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine Reward and Relapse: Preclinical Findings

Panlilio

Justinová

Mascia

et al. 2012

Neuropsychopharmacol

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Experimental drugs that activate a-type peroxisome proliferator-activated receptors (PPARa) have recently been shown to reduce the rewarding effects of nicotine in animals, but these drugs have not been approved for human use. The fibrates are a class of PPARa-activating medications that are widely prescribed to improve lipid profiles and prevent cardiovascular disease, but these drugs have not been tested in animal models of nicotine reward. Here, we examine the effects of clofibrate, a representative of the fibrate class, on reward-related behavioral, electrophysiological, and neurochemical effects of nicotine in rats and squirrel monkeys. Clofibrate prevented the acquisition of nicotine-taking behavior in naive animals, substantially decreased nicotine taking in experienced animals, and counteracted the relapse-inducing effects of re-exposure to nicotine or nicotine-associated cues after a period of abstinence. In the central nervous system, clofibrate blocked nicotine's effects on neuronal firing in the ventral tegmental area and on dopamine release in the nucleus accumbens shell. All of these results suggest that fibrate medications might promote smoking cessation. The fact that fibrates are already approved for human use could expedite clinical trials and subsequent implementation of fibrates as a treatment for tobacco dependence, especially in smokers with abnormal lipid profiles.

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“…Figure 1A shows an example of the pattern of cocaine selfadministration on a PR schedule. The first response of the session results in an intravenous cocaine infusion; thereafter the delivery of this reinforcer is contingent upon an increasing number of responses incremented through the following series: 1, 2, 4,6,9,12,15,20,25,32,40,50,62,77,95,118,145,178,219,268,328,402,492, 603, etc. [9].…”

Section: Progressive Ratio Training and Final Ratio Escalationmentioning

confidence: 99%

“…It should be emphasized, however, that the two dependent measures are very different. Final ratios reflect some measure of the motivation to obtain drug, while rate of drug intake on an FR1 schedule of reinforcement reflects the blood or brain level at which an animal will titrate its intake [46,47,48,49] but see also [50]. These are very different concepts.…”

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confidence: 99%

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

Oleson

Roberts

2008

Drug Discovery Today: Disease Models

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Investigators who study drug addiction are fortunate to have access to excellent animal models. Such models will be invaluable in the assessment of factors involved in the progression of drug addiction. The relevance of these findings, however, will depend on the general understanding of how each model is related to drug addiction. The present review focuses on several procedures that were designed to model the addiction process and questions whether these models are tapping into the same underlying process or whether each is addressing a unique feature. Furthermore, various factors (e.g., rate of drug onset, dose magnitude, early drug history, periods of abstinence) influencing the progression of these addiction-like changes in behavior are discussed. KeywordsCocaine; Escalation; Motivation; Sensitization; Tolerance; Self Administration A better understanding of the neurobiology of drug addiction is beginning to emerge through the analysis of brain changes in individuals addicted to drugs. Recent advances in neuroimaging have shown activation of specific brain regions associated with drug craving (see reviews, [1,2]). Chronic drug abuse has also been shown to cause changes in brain structure and function (see reviews, [3,4,5]). Additional advancements in the application of molecular biology techniques has provided important post-mortem analyses of brain tissue from addicts (see reviews, [6,7]).There are, however, many limitations and challenges associated with studying drug addiction in human subjects. Various confounding factors exist within samples of drug addicts that may be difficult to parse apart, such as differences in environment, genetics, poly-drug use and route of administration. Attrition is also a concern due to the general social instability associated with drug addicts. Moreover, various ethical dilemmas may restrict the experimental design of longitudinal studies and the administration of pharmacological treatments to illicit drug users.*Corresponding Author: David C.S. Roberts, Ph.D., Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, Tel: (336) Fax: (336) 716-8501, dscrobts@wfubmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Animal studies offer an opportunity to investigate specific aspects of the addiction process without the confounding factors associated with human studies. As this special issue of Drug Discovery Today attests, a variety of animal models have been developed which can be used to address fundamental issues related to drug abuse and de...

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Variability of drug self-administration in rats

Cited by 65 publications

References 55 publications

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Previous Exposure to THC Alters the Reinforcing Efficacy and Anxiety-Related Effects of Cocaine in Rats

Novel Use of a Lipid-Lowering Fibrate Medication to Prevent Nicotine Reward and Relapse: Preclinical Findings

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

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