Leigh Panlilio, Ph.D.

@article{Panlilio:2019aa,

title = {Stress, craving and mood as predictors of early dropout from opioid agonist therapy.},

author = {Leigh V Panlilio and Samuel W Stull and William J Kowalczyk and Karran A Phillips and Jennifer R Schroeder and Jeremiah W Bertz and Massoud Vahabzadeh and Jia-Ling Lin and Mustapha Mezghanni and Edward V Nunes and David H Epstein and Kenzie L Preston},

url = {https://www.ncbi.nlm.nih.gov/pubmed/31357121},

doi = {10.1016/j.drugalcdep.2019.05.026},

issn = {1879-0046 (Electronic); 0376-8716 (Linking)},

year  = {2019},

date = {2019-09-01},

journal = {Drug Alcohol Depend},

volume = {202},

pages = {200--208},

address = {Intramural Research Program, National Institute on Drug Abuse, 251 Bayview Blvd., Suite 200, Baltimore, MD, 21224, USA.},

abstract = {BACKGROUND: Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods - which take many repeated measurements over time, usually in the field- have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. METHODS: Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. RESULTS: Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. CONCLUSIONS: Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.},

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}

@article{Panlilio:2017aa,

title = {Preclinical Studies of Cannabinoid Reward, Treatments for Cannabis Use Disorder, and Addiction-Related Effects of Cannabinoid Exposure.},

author = {Leigh V Panlilio and Zuzana Justinova},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28845848},

doi = {10.1038/npp.2017.193},

issn = {1740-634X (Electronic); 0893-133X (Linking)},

year  = {2017},

date = {2017-08-28},

journal = {Neuropsychopharmacology},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA.},

abstract = {Cannabis use has become increasingly accepted socially and legally, for both recreational and medicinal purposes. Without reliable information about the effects of cannabis, people cannot make informed decisions regarding its use. Like alcohol and tobacco, cannabis can have serious adverse effects on health, and some people have difficulty discontinuing their use of the drug. Many cannabis users progress to using and becoming addicted to other drugs, but the reasons for this progression are unclear. The natural cannabinoid system of the brain is complex and involved in many functions, including brain development, reward, emotion, and cognition. Animal research provides an objective and controlled means of obtaining information about: (1) how cannabis affects the brain and behavior, (2) whether medications can be developed to treat cannabis use disorder, and (3) whether cannabis might produce lasting changes in the brain that increase the likelihood of becoming addicted to other drugs. This review explains the tactics used to address these issues, evaluates the progress that has been made, and offers some directions for future research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Secci:2016aa,

title = {Choice between delayed food and immediate oxycodone in rats.},

author = {Maria E Secci and Julie A Factor and Charles W Schindler and Leigh V Panlilio},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27678551},

doi = {10.1007/s00213-016-4429-0},

issn = {1432-2072 (Electronic); 0033-3158 (Linking)},

year  = {2016},

date = {2016-12-01},

journal = {Psychopharmacology (Berl)},

volume = {233},

number = {23-24},

pages = {3977--3989},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, 251 Bayview Blvd, Baltimore, MD, USA.},

abstract = {RATIONALE: The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. OBJECTIVES: To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 mug/kg) and delayed delivery of palatable food pellets. RESULTS: Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. CONCLUSIONS: These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2013aa,

title = {Prior exposure to THC increases the addictive effects of nicotine in rats.},

author = {Leigh V Panlilio and Claudio Zanettini and Chanel Barnes and Marcelo Solinas and Steven R Goldberg},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23314220},

doi = {10.1038/npp.2013.16},

issn = {1740-634X (Electronic); 0893-133X (Linking)},

year  = {2013},

date = {2013-06-01},

journal = {Neuropsychopharmacology},

volume = {38},

number = {7},

pages = {1198--1208},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, Department of Health and Human Services, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA.},

abstract = {Although it is more common for drug abuse to progress from tobacco to cannabis, in many cases cannabis use develops before tobacco use. Epidemiological evidence indicates that prior cannabis use increases the likelihood of becoming dependent on tobacco. To determine whether this effect might be due to cannabis exposure per se, in addition to any genetic, social, or environmental factors that might contribute, we extended our series of studies on 'gateway drug' effects in animal models of drug abuse. Rats were exposed to THC, the main psychoactive constituent of cannabis, for 3 days (two intraperitoneal injections/day). Then, starting 1 week later, they were allowed to self-administer nicotine intravenously. THC exposure increased the likelihood of acquiring the nicotine self-administration response from 65% in vehicle-exposed rats to 94% in THC-exposed rats. When the price of nicotine was manipulated by increasing the response requirement, THC-exposed rats maintained higher levels of intake than vehicle-exposed rats, indicating that THC exposure increased the value of nicotine reward. These results contrast sharply with our earlier findings that prior THC exposure did not increase the likelihood of rats acquiring either heroin or cocaine self-administration, nor did it increase the reward value of these drugs. The findings obtained here suggest that a history of cannabis exposure might have lasting effects that increase the risk of becoming addicted to nicotine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2012aa,

title = {Combined effects of THC and caffeine on working memory in rats.},

author = {Leigh V Panlilio and Sergi Ferre and Sevil Yasar and Eric B Thorndike and Charles W Schindler and Steven R Goldberg},

url = {https://www.ncbi.nlm.nih.gov/pubmed/21699509},

doi = {10.1111/j.1476-5381.2011.01554.x},

issn = {1476-5381 (Electronic); 0007-1188 (Linking)},

year  = {2012},

date = {2012-04-01},

journal = {Br J Pharmacol},

volume = {165},

number = {8},

pages = {2529--2538},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov},

abstract = {BACKGROUND AND PURPOSE: Cannabis and caffeine are two of the most widely used psychoactive substances. Delta(9) -Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, induces deficits in short-term memory. Caffeine, a non-selective adenosine receptor antagonist, attenuates some memory deficits, but there have been few studies addressing the effects of caffeine and THC in combination. Here, we evaluate the effects of these drugs using a rodent model of working memory. EXPERIMENTAL APPROACH: Rats were given THC (0, 1 and 3 mg.kg(-1) , i.p.) along with caffeine (0, 1, 3 and 10 mg.kg(-1) , i.p.), the selective adenosine A(1) -receptor antagonist CPT (0, 3 and 10 mg.kg(-1) ) or the selective adenosine A(2A) -receptor antagonist SCH58261 (0 and 5 mg.kg(-1) ) and were tested with a delayed non-matching-to-position procedure in which behaviour during the delay was automatically recorded as a model of memory rehearsal. KEY RESULTS: THC alone produced memory deficits at 3 mg.kg(-1) . The initial exposure to caffeine (10 mg.kg(-1) ) disrupted the established pattern of rehearsal-like behaviour, but tolerance developed rapidly to this effect. CPT and SCH58261 alone had no significant effects on rehearsal or memory. When a subthreshold dose of THC (1 mg.kg(-1) ) was combined with caffeine (10 mg.kg(-1) ) or CPT (10 mg.kg(-1) ), memory performance was significantly impaired, even though performance of the rehearsal-like pattern was not significantly altered. CONCLUSION AND IMPLICATIONS: Caffeine did not counteract memory deficits induced by THC but actually exacerbated them. These results are consistent with recent findings that adenosine A(1) receptors modulate cannabinoid signalling in the hippocampus. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.},

keywords = {},

pubstate = {published},

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}

@article{Panlilio:2008ab,

title = {A stimulus-control account of regulated drug intake in rats.},

author = {Leigh V Panlilio and Eric B Thorndike and Charles W Schindler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/17957355},

doi = {10.1007/s00213-007-0978-6},

issn = {0033-3158 (Print); 0033-3158 (Linking)},

year  = {2008},

date = {2008-02-01},

journal = {Psychopharmacology (Berl)},

volume = {196},

number = {3},

pages = {441--450},

address = {National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov},

abstract = {RATIONALE: Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not. OBJECTIVE: This hypothetical stimulus control aspect of drug self-administration was emulated using a schedule of food reinforcement. MATERIALS AND METHODS: Rats' nose-poke responses produced food only when a cue light was present. No drug was administered at any time. However, the state of the light stimulus was determined by calculating what the whole-body drug level would have been if each response in the session had produced a drug injection. The light was only presented while this virtual drug level was below a specific threshold. A range of doses of cocaine and remifentanil were emulated using parameters based on previous self-administration experiments. RESULTS: Response patterns were highly regular, dose-dependent, and remarkably similar to actual drug self-administration. CONCLUSION: This similarity suggests that the emulation schedule may provide a reasonable model of the contingencies inherent in drug reinforcement. Thus, these results support a stimulus control account of regulated drug intake in which rats learn to discriminate when the level of drug effect has fallen to a point where another self-injection will be reinforcing.},

keywords = {},

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tppubtype = {article}

}

@article{Panlilio:2007ad,

title = {Self-administration of drugs in animals and humans as a model and an investigative tool.},

author = {Leigh V Panlilio and Steven R Goldberg},

url = {https://www.ncbi.nlm.nih.gov/pubmed/18031422},

doi = {10.1111/j.1360-0443.2007.02011.x},

issn = {0965-2140 (Print); 0965-2140 (Linking)},

year  = {2007},

date = {2007-12-01},

journal = {Addiction},

volume = {102},

number = {12},

pages = {1863--1870},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, Baltimore, MD 21224, USA.},

abstract = {AIM: To review briefly the methods, assumptions, models, accomplishments, drawbacks and future directions of research using drug self-administration in animals and humans. BACKGROUND: The use of drug self-administration to study addiction is based on the assumption that drugs reinforce the behavior that results in their delivery. A wide range of drug self-administration techniques have been developed to model specific aspects of addiction. These techniques are highly amenable to being combined with a wide variety of neuroscience techniques. CONCLUSIONS: The identification of drug use as behavior that is reinforced by drugs has contributed greatly to the understanding and treatment of addiction. As part of a program of pre-clinical research that also involves screening with a variety of simpler behavioral techniques, drug self-administration procedures can provide an important last step in testing potential treatments for addiction. There is currently a concerted effort to develop self-administration procedures that model the extreme nature of the behavior engendered by addiction. As advances continue to be made in neuroscience techniques, self-administration should continue to provide a means of applying these techniques within a sophisticated and valid model of human drug addiction.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2005ab,

title = {Human cocaine-seeking behavior and its control by drug-associated stimuli in the laboratory.},

author = {Leigh V Panlilio and Sevil Yasar and Ro Nemeth-Coslett and Jonathan L Katz and Jack E Henningfield and Marcello Solinas and Stephen J Heishman and Charles W Schindler and Steven R Goldberg},

url = {https://www.ncbi.nlm.nih.gov/pubmed/15536497},

doi = {10.1038/sj.npp.1300599},

issn = {0893-133X (Print); 0893-133X (Linking)},

year  = {2005},

date = {2005-02-01},

journal = {Neuropsychopharmacology},

volume = {30},

number = {2},

pages = {433--443},

address = {Preclinical Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, USA.},

abstract = {Second-order schedules of drug self-administration were developed to incorporate the effects of drug-related environmental stimuli into an animal model of drug abuse, making it more similar to human situations. Ironically, little is known about how human subjects behave under these schedules. In this study, human volunteers with a history of cocaine use worked on a second-order schedule in which every 100th lever response produced an auditory-visual brief stimulus (2 s). The first stimulus produced after 1 h was extended to 10 s and paired with an intravenous injection of cocaine (25 mg). Up to three injections were allowed per session. In different phases of the experiment, presentation of the brief stimulus was discontinued and/or saline solution (placebo) was injected instead of cocaine. Injections of cocaine were found to maintain responding even when the brief stimulus was not presented. Placebo injections alone did not maintain responding. In contrast, the brief stimulus maintained high levels of responding under placebo conditions, even though self-reports indicated that subjects could clearly discriminate that they were not receiving cocaine. These results demonstrate that drug-related environmental stimuli can maintain persistent drug seeking during periods of drug unavailability. As this procedure directly measures the effects of stimuli on drug seeking, it may provide a valuable complement to indirect measures, such as self-reports of craving, that are often used with human subjects. The similarity of the response patterns in humans and animals also supports the use of second-order schedules in animals as a valid model of human drug seeking.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2003aa,

title = {Reinstatement of punishment-suppressed opioid self-administration in rats: an alternative model of relapse to drug abuse.},

author = {Leigh V Panlilio and Eric B Thorndike and Charles W Schindler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/12845420},

doi = {10.1007/s00213-002-1193-0},

issn = {0033-3158 (Print); 0033-3158 (Linking)},

year  = {2003},

date = {2003-07-01},

journal = {Psychopharmacology (Berl)},

volume = {168},

number = {1-2},

pages = {229--235},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA, USA. lpanlili@intra.nida.nih.gov.},

abstract = {RATIONALE: Animal models of relapse to drug abuse typically assess the ability of various manipulations to reinstate responding that has ceased due to non-reinforcement (extinction). However, there is a lack of information concerning the reinstatement of responding that has ceased for reasons other than extinction. OBJECTIVES: This study examined the ability of response-independent reinforcer delivery (priming) to reinstate food- or drug-reinforced responding that had been suppressed by response-contingent footshock (punishment). METHODS: Nose-poke responding by separate groups of rats was reinforced with food (45 mg/delivery) or intravenous remifentanil (4 micro g/kg per infusion), a short-acting micro -opioid agonist. After either 3 or 27 days of training (with 100 reinforcers/day), a punishment contingency was introduced that rapidly suppressed responding. Then, the punishment contingency was discontinued, and half the rats received priming. RESULTS: Priming by non-contingent delivery of food or remifentanil significantly reduced the number of sessions required for responding to resume. There were no significant differences in this effect between short-term and long-term training or between food- and drug-trained groups. CONCLUSIONS: Self-administration responding that has been suppressed by punishment can be reinstated by priming, and it can eventually resume even without priming. Under the conditions studied here, priming after punishment had effects qualitatively similar to those typically seen after extinction. This punishment/reinstatement procedure may be useful for comparing the effects of other manipulations known to affect behavior in the extinction/reinstatement model of relapse.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2003aab,

title = {Variability of drug self-administration in rats.},

author = {Leigh V Panlilio and Jonathan L Katz and Roy W Pickens and Charles W Schindler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/12644888},

doi = {10.1007/s00213-002-1366-x},

issn = {0033-3158 (Print); 0033-3158 (Linking)},

year  = {2003},

date = {2003-04-01},

journal = {Psychopharmacology (Berl)},

volume = {167},

number = {1},

pages = {9--19},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov},

abstract = {RATIONALE: Although temporal patterns of drug self-administration in animals are known to be highly regular, this regularity has rarely been quantified or systematically compared across reinforcers. OBJECTIVES: Over a range of unit doses, this study assessed: (1) the within-subject variability of inter-infusion intervals (latencies); (2) the estimated whole-body drug level at the time of self-infusion; (3) the within-subject variability of these drug levels; and (4) the statistical dependence between successive latencies, to determine whether regularity is maintained by compensatory, moment-to-moment adjustment of latencies. METHODS: Rats were trained with cocaine (10-1000 microg/kg per infusion, IV), remifentanil (an ultra-short acting opioid; 0.25-32 microg/kg per infusion, IV), or food (20-180 mg/delivery). RESULTS: Within subjects, latencies were most consistent from infusion to infusion at unit doses on the descending limb of the dose-response curve. However, the drug level at the time an infusion was initiated was actually least consistent at these doses. Sequential latencies showed only a weak autocorrelation for both drugs. CONCLUSION: These results suggest that highly consistent response patterns are not simply a product of precise titration of drug levels. The weak autocorrelation between sequential latencies suggests that temporal regularity of responding is not maintained through compensatory adjustments of post-infusion pauses.},

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pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2000aab,

title = {Self-administration of remifentanil, an ultra-short acting opioid, under continuous and progressive-ratio schedules of reinforcement in rats.},

author = {L V Panlilio and C W Schindler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/10867977},

doi = {10.1007/s002130000415},

issn = {0033-3158 (Print); 0033-3158 (Linking)},

year  = {2000},

date = {2000-05-01},

journal = {Psychopharmacology (Berl)},

volume = {150},

number = {1},

pages = {61--66},

address = {Preclinical Pharmacology Section, National Institute on Drug Abuse, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov},

abstract = {RATIONALE: Remifentanil is a mu-opioid agonist with an exceptionally short duration of action. Evaluating remifentanil's effects within the self-administration model of drug abuse may provide insight into the relationship between a drug's duration of action and its effectiveness as a reinforcer. OBJECTIVES: This study was conducted to establish a dose-effect function for intravenous remifentanil self-administration in rats and to assess the drug's ability to maintain responding under intermittent schedules of reinforcement. METHODS: Inter-infusion intervals were recorded under two continuous-reinforcement schedules of remifentanil self-administration. In the fixed-dose schedule, the unit dose (0.25-32 micrograms/kg) was held constant within sessions but varied across sessions. In the variable-dose schedule, four different doses were self-administered in random order within each session. For comparison, heroin (6.25-125 micrograms/kg) was studied with the variable-dose schedule. Remifentanil and heroin were also compared under a progressive-ratio schedule of reinforcement in which the response requirements increased exponentially with each successive infusion until responding ceased within each session. RESULTS: Under the continuous-reinforcement schedules, inter-infusion intervals for both drugs increased monotonically as a function of dose, with the remifentanil curve being considerably flatter. Under the progressive-ratio schedule, breaking points varied as an inverted-U shaped function, and the highest breaking points maintained by remifentanil and heroin were similar. At the doses that maintained the highest breaking points under the progressive-ratio schedule, post-infusion pauses under the continuous-reinforcement schedule were about three times shorter with remifentanil than with heroin. CONCLUSIONS: Although rates of self-administration are clearly influenced by a drug's duration of action, the ability to maintain responding under intermittent schedules of reinforcement may be independent of duration of action.},

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pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:2000aa,

title = {Effects of compounding drug-related stimuli: escalation of heroin self-administration.},

author = {L V Panlilio and S J Weiss and C W Schindler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/10784010},

doi = {10.1901/jeab.2000.73-211},

issn = {0022-5002 (Print); 0022-5002 (Linking)},

year  = {2000},

date = {2000-03-01},

journal = {J Exp Anal Behav},

volume = {73},

number = {2},

pages = {211--224},

address = {Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. lpanlili@intra.nida.nih.gov},

abstract = {Previous experiments have demonstrated that presenting independently established discriminative stimuli in compound can substantially increase operant responding maintained by food reinforcement or shock avoidance. Recently, this phenomenon was also shown to occur with cocaine self-administration. The present study further assessed the generality of these stimulus-compounding effects by systematically replicating them with heroin self-administration. Rats' nose-poke responses produced intravenous heroin (0.025 mg/kg per infusion) on a variable-ratio schedule when either a tone or a light was present. In the absence of these stimuli, responding was not reinforced. Once discriminative control by the tone and light had been established, the stimuli were presented in compound under extinction (with heroin discontinued) or maintenance conditions (with heroin available during test-stimulus presentations). In extinction, the tone-light compound increased responding approximately threefold compared to tone or light alone. Under maintenance conditions, compounding increased heroin intake approximately twofold. These effects closely matched those obtained earlier with cocaine. This consistency across pharmacological classes and across drug and nondrug reinforcers further confirms that (a) self-administered drugs support conditioning and learning in a manner similar to that supported by other reinforcers; and (b) multiple drug-related cues interact in lawful and predictable ways to affect drug seeking and consumption.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Panlilio:1996aa,

title = {Cocaine self-administration increased by compounding discriminative stimuli.},

author = {L V Panlilio and S J Weiss and C W Schindler},

url = {https://www.ncbi.nlm.nih.gov/pubmed/8815954},

doi = {10.1007/bf02247329},

issn = {0033-3158 (Print); 0033-3158 (Linking)},

year  = {1996},

date = {1996-06-01},

journal = {Psychopharmacology (Berl)},

volume = {125},

number = {3},

pages = {202--208},

address = {Preclinical Pharmacology Laboratory, National Institutes of Health, National Institute on Drug Abuse, Baltimore, MD 21224, USA.},

abstract = {Presenting independently established discriminative stimuli in compound can substantially increase response rates under food and shock-avoidance schedules. To determine whether this effect extends to drug self-administration, rats were trained to press a lever to receive cocaine intravenously. A tone and a light were independently established as discriminative stimuli for cocaine self-administration, then presented in combination in a stimulus-compounding test. Compared to tone and light alone, the tone-plus-light compound stimulus increased responding approximately three-fold when cocaine was withheld during testing, and it increased drug intake approximately two-fold when cocaine was made available during testing. Compounding did not increase responding after training in a truly random control condition where tone and light were presented uncorrelated with the availability of cocaine. The results obtained with this animal model of drug abuse define conditions under which combinations of environmental stimuli might substantially increase human drug use.},

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tppubtype = {article}

}