The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
S. Stevens Negus - One of the best experts on this subject based on the ideXlab platform.
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Opioid Antagonist Effects in Animal Models Related to Opioid Abuse: Drug Discrimination and Drug Self-Administration
Opiate Receptors and Antagonists, 2020Co-Authors: S. Stevens NegusAbstract:Preclinical assays of Drug discrimination and Drug Self-Administration are widely used to examine abuse-related Drug effects, and opioid antagonists have been extensively studied in these procedures. Studies with opioid antagonists have served two general purposes. First, antagonists selective for mu, kappa and delta receptors have been used as tools to characterize the pharmacological and neuroanatomical mechanisms that underlie the discriminative stimulus and reinforcing effects of opioids. Studies with antagonists have contributed to evidence suggesting that activation of central mu, kappa or delta receptors can mediate robust and receptor-selective discriminative stimulus effects. Conversely, the reinforcing effects of opioids in assays of Drug Self-Administration appear to rely primarily on central mu receptor activation. A second rationale for antagonist studies has been to examine factors that may influence antagonist utility in the treatment of opioid abuse and dependence. In non-dependent animals, opioid antagonists such as naltrexone effectively block the discriminative stimulus and reinforcing effects of abused opioid agonists while producing minimal side effects. However, opioid antagonists themselves produce weak discriminative stimulus effects and do not function as positive reinforcers. In opioid-dependent animals, opioid antagonists precipitate withdrawal, readily function as negative reinforcers that engender avoidance/escape behaviours, and increase the reinforcing efficacy of opioid agonists. These factors likely contribute to the poor compliance with opioid antagonists observed in clinical studies. Compliance could be improved by integrating antagonist treatment into behaviours maintained by other stimuli (e.g. contingency management) or by using very long-acting opioid antagonist formulations to reduce the frequency required for antagonist administration.
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Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration
Advances in Pharmacological Sciences, 2012Co-Authors: Matthew L. Banks, S. Stevens NegusAbstract:Drug Self-Administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous Drug Self-Administration. The aims of this paper are to first highlight the evolution of Drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of Drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of Drugs in assays of Drug Self-Administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of Drug choice procedures.
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Interactions between δ and μ Opioid Agonists in Assays of Schedule-Controlled Responding, Thermal Nociception, Drug Self-Administration, and Drug versus Food Choice in Rhesus Monkeys: Studies with SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Glenn W. Stevenson, John E. Folk, Kenner C. Rice, S. Stevens NegusAbstract:Interactions between δ and μ opioid agonists in rhesus monkeys vary as a function of the behavioral endpoint. The present study compared interactions between the δ agonist SNC80 [(+)-4-[(α R )-α-((2 S ,5 R )-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N , N -diethylbenzamide] and the μ agonist heroin in assays of schedule-controlled responding, thermal nociception, and Drug Self-Administration. Both SNC80 (ED 50 = 0.43 mg/kg) and heroin (ED 50 = 0.088 mg/kg) produced a dose-dependent and complete suppression of response rates in the assay of schedule-controlled responding. Heroin also produced thermal antinociception (ED 5°C = 0.18 mg/kg) and maintained Drug Self-Administration under both a fixed ratio schedule [dose-effect curve peak at 0.0032 mg/kg/injection (inj)] and under a food versus heroin concurrent-choice schedule (ED 50 = 0.013 mg/kg/inj), whereas SNC80 did not produce thermal antinociception or maintain Self-Administration. Fixed ratio mixtures of SNC80 and heroin (1.6:1, 4.7:1, and 14:1 SNC80/heroin) produced additive effects in the assay of schedule-controlled responding and superadditive effects in the assay of thermal nociception. Also, SNC80 did not enhance the reinforcing effects of heroin, indicating that mixtures of SNC80 and heroin produced additive or infra-additive reinforcing effects. These results provide additional evidence to suggest that δ/μ interactions depend on the experimental endpoint and further suggest that δ agonists may selectively enhance the antinociceptive effects of μ agonists while either not affecting or decreasing the sedative and reinforcing effects of μ agonists.
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Preclinical Evaluation of Pharmacotherapies for Treatment of Cocaine and Opioid Abuse Using Drug Self-Administration Procedures
Neuropsychopharmacology, 1996Co-Authors: Nancy K Mello, S. Stevens NegusAbstract:Drug abuse is a major public health problem, and the relationship between intravenous Drug abuse and AIDS underscores the need for more effective treatment medications. Animal models of Drug Self-Administration are useful to systematically evaluate new treatment medications and predict clinical efficacy. This review summarizes the status of preclinical evaluations of medications for treatment of cocaine and opiate abuse. The basic Drug Self-Administration methodology and the rationale for experimental designs and outcome criteria are described. Studies of the effects of dopamine or opioid receptor agonists and antagonists as well as medications used clinically for other indications on Drug Self-Administration are critically examined. Where possible, the degree of concordance between clinical and preclinical studies of Drug abuse treatment medications is discussed. We conclude that Drug Self-Administration models are valuable for preclinical assessment of medication efficacy, and we recommend some strategies to further improve evaluation procedures. The discovery of more effective medications for substance abuse treatment should be facilitated by recent advances in behavioral science, pharmacology, neurobiology and medicinal chemistry.
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Diurnal patterns of cocaine and heroin Self-Administration in rhesus monkeys responding under a schedule of multiple daily sessions.
Behavioural Pharmacology, 1995Co-Authors: S. Stevens Negus, Nancy K Mello, Scott E. Lukas, Jack H. MendelsonAbstract:: A number of non-pharmacological factors have been shown to influence Drug Self-Administration in experimental animals. This report examines diurnal changes in Drug Self-Administration by rhesus monkeys trained to self-administer food (1gm fruit-flavored pellets) and cocaine (0.01 or 0.032mg/kg/injection) under a second order FR4 (VR16:S) schedule during four daily food and Drug Self-Administration sessions. Saline, different unit doses of cocaine (0.001-0.1mg/kg/injection) or different unit doses of heroin (0.0001-0.01mg/kg/injection) were substituted for the maintenance dose of cocaine during Drug sessions. Dose-effect curves relating unit dose of cocaine or heroin to the number of injections per session displayed an inverted U-shape during each of the four daily Drug sessions. When 0.032mg/kg/injection cocaine or 0.0032mg/kg/injection heroin were available, monkeys usually self-administered the maximum number of injections during all four Drug sessions. Substitution of saline or lower unit doses of cocaine (0.001-0.01mg/kg/injection) or heroin (0.0001-0.001mg/kg/injection) decreased the number of injections/session; however, these decreases were consistently greater during the evening (20.00-21.00h) and morning (07.00-08.00h) sessions than during the afternoon sessions (12.00-13.00h and 16.00-17.00h). As a result, the ascending limbs of the cocaine and heroin dose-effect curves for the evening and morning sessions were shifted to the right of the ascending limbs of the dose-effect curves for the afternoon sessions. Moreover, when saline was substituted for cocaine for only two sessions per day, Drug Self-Administration decreased more during the evening and morning sessions even when the cocaine was available during those sessions. These findings suggest a diurnal variation in cocaine and heroin Self-Administration. Specifically, Drug Self-Administration during the evening and morning sessions appears to be more sensitive to a decrease in reinforcer magnitude than responding during the afternoon sessions. These findings confirm and extend previous reports of the influence of non-pharmacological factors on Drug Self-Administration.
Mark A. Smith - One of the best experts on this subject based on the ideXlab platform.
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The effects of sex, estrous cycle, and social contact on cocaine and heroin Self-Administration in rats
Psychopharmacology, 2016Co-Authors: Ryan T. Lacy, Justin C. Strickland, Max Feinstein, Andrea M. Robinson, Mark A. SmithAbstract:Rationale Preclinical studies indicate that gonadal hormones are important determinants of Drug Self-Administration. To date, little is known about the influence of sex and estrous cycle on Drug Self-Administration in ecologically relevant social contexts.
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Animal models of social contact and Drug Self-Administration.
Pharmacology Biochemistry and Behavior, 2015Co-Authors: Justin C. Strickland, Mark A. SmithAbstract:Social learning theories of Drug abuse propose that individuals imitate Drug use behaviors modeled by social peers, and that these behaviors are selectively reinforced and/or punished depending on group norms. Historically, animal models of social influence have focused on distal factors (i.e., those factors outside the Drug-taking context) in Drug Self-Administration studies. Recently, several investigators have developed novel models, or significantly modified existing models, to examine the role of proximal factors (i.e., those factors that are immediately present at the time of Drug taking) on measures of Drug Self-Administration. Studies using these newer models have revealed several important conclusions regarding the effects of social learning on Drug abuse: 1) the presence of a social partner influences Drug Self-Administration, 2) the behavior of a social partner determines whether social contact will increase or decrease Drug intake, and 3) social partners can model and imitate specific patterns of Drug Self-Administration. These findings are congruent with those obtained in the human laboratory, providing support for the cross-species generality and validity of these preclinical models. This mini-review describes in detail some of the preclinical animal models used to study social contact and Drug Self-Administration to guide future research on social learning and Drug abuse.
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Social preference and Drug Self-Administration: A preclinical model of social choice within peer groups
Drug and Alcohol Dependence, 2013Co-Authors: Mark A. Smith, Elizabeth G. PittsAbstract:Abstract Background selection models of substance use propose that individuals choose or self-select into peer groups based on shared substance use histories. Few experimental studies have examined the role of selection in substance use, possibly because few preclinical models allow subjects to choose or select individuals based on a shared Self-Administration history. Methods In the present study, we used custom-built, three-compartment, operant conditioning chambers that permitted multiple rats to self-administer cocaine simultaneously in the same session. Rats assigned to the center compartment had access to two response levers, each in close physical proximity to one of its partners. In one group, a rat with access to cocaine was assigned to the center compartment and flanked by one rat with access to cocaine and one rat without access. In a second group, a rat without access to cocaine was assigned to the center compartment and flanked by one rat with access to cocaine and one rat without access. Results In the first group, rats with access to cocaine emitted more responses on the lever in close proximity to the other rat with access to cocaine; in the second group, rats without access to cocaine emitted more responses on the lever in close proximity to the other rat without access. These preferences were not apparent immediately but developed gradually over the course of several days of testing. Conclusion These data suggest that rats prefer to be in close physical proximity to another rat with a shared behavioral history during periods of Drug Self-Administration.
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Peer influences on Drug Self-Administration: social facilitation and social inhibition of cocaine intake in male rats.
Psychopharmacology, 2012Co-Authors: Mark A. SmithAbstract:Rationale One problem facing animal models of intravenous Drug Self-Administration, particularly those examining social manipulations, is that subjects must be removed from the home environment and separated from cagemates during testing. This represents a limitation of animal models because it fails to capture the complex social environments in which Drug use often occur.
Roger D. Spealman - One of the best experts on this subject based on the ideXlab platform.
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Current Protocols in Neuroscience - Intravenous Self-Administration techniques in monkeys.
Current protocols in protein science, 2020Co-Authors: Donna M. Platt, Galen Carey, Roger D. SpealmanAbstract:: Drug Self-Administration is a procedure in which a subject performs a response, called an operant, that results in the delivery of a Drug injection. This procedure is viewed as a relevant model for the study of human Drug-taking behavior. Drug Self-Administration in primates has several characteristics that resemble Drug-taking behavior in humans, and Drugs that are commonly abused by humans also typically maintain Self-Administration behavior in monkeys. Drug Self-Administration procedures allow for the study of a variety of Drug properties. For instance, they are used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of Drug addiction. These procedures also can be used to study the process of Drug reinforcement. This unit describes intravenous Drug Self-Administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.
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Intravenous Self-Administration techniques in monkeys.
Current protocols in neuroscience, 2020Co-Authors: Donna M. Platt, Galen Carey, Roger D. SpealmanAbstract:Drug Self-Administration is a procedure in which a subject performs a response, called an operant, that results in the delivery of a Drug injection. This procedure is viewed as a relevant model for the study of human Drug-taking behavior. Drug Self-Administration in primates has several characteristics that resemble Drug-taking behavior in humans, and Drugs that are commonly abused by humans also typically maintain Self-Administration behavior in monkeys. Drug Self-Administration procedures allow for the study of a variety of Drug properties. For instance, they are used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of Drug addiction. These procedures also can be used to study the process of Drug reinforcement. This unit describes intravenous Drug Self-Administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.
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Models of neurological disease (substance abuse): Self-Administration in monkeys.
Current protocols in pharmacology, 2020Co-Authors: Donna M. Platt, Galen Carey, Roger D. SpealmanAbstract:Drug Self-Administration is a procedure in which a subject performs a specified response that results in the delivery of a Drug injection. This procedure is viewed as a relevant model for the study of human Drug-taking behavior. Drug Self-Administration in primates has several characteristics that resemble Drug-taking behavior in humans, and agents commonly abused by humans also generally maintain Self-Administration behavior in monkeys. Self-Administration procedures allow for the study of a variety of Drug properties. For instance, they can be used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of Drug addiction. These procedures can also be employed for examining Drug reinforcement mechanisms. Described in this unit are procedures for studying intravenous Drug Self-Administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.
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Current Protocols in Pharmacology - Models of Neurological Disease (Substance Abuse): Self-Administration in Monkeys
Current protocols in pharmacology, 2012Co-Authors: Donna M. Platt, Galen Carey, Roger D. SpealmanAbstract:Drug Self-Administration is a procedure in which a subject performs a specified response that results in the delivery of a Drug injection. This procedure is viewed as a relevant model for the study of human Drug-taking behavior. Drug Self-Administration in primates has several characteristics that resemble Drug-taking behavior in humans, and agents commonly abused by humans also generally maintain Self-Administration behavior in monkeys. Self-Administration procedures allow for the study of a variety of Drug properties. For instance, they can be used to investigate the abuse potential of new compounds and to study the effects of candidate medications for the treatment of Drug addiction. These procedures also can be employed for examining Drug reinforcement mechanisms. Described in this unit are procedures for studying intravenous Drug Self-Administration in large primates, such as rhesus macaques, and smaller primates, such as squirrel monkeys.
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Controversies in translational research: Drug Self-Administration
Psychopharmacology, 2008Co-Authors: Margaret Haney, Roger D. SpealmanAbstract:Rationale Laboratory animal and human models of Drug Self-Administration are used to evaluate potential pharmacotherapies for Drug abuse, yet the utility of these models in predicting clinically useful medications is variable.
Steven R. Goldberg - One of the best experts on this subject based on the ideXlab platform.
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Self‐administration of Drugs in animals and humans as a model and an investigative tool
Addiction, 2007Co-Authors: Leigh V. Panlilio, Steven R. GoldbergAbstract: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.
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Second-order schedules of Drug Self-Administration in animals.
Psychopharmacology, 2002Co-Authors: Charles W. Schindler, Leigh V. Panlilio, Steven R. GoldbergAbstract:On a second-order schedule, a subject responds according to one schedule (the unit schedule) for a brief presentation of a stimulus such as a light. Responding by the subject on this unit schedule is then reinforced according to another schedule of reinforcement. Second-order schedules of Drug injection allow the study of more complex behavioral sequences than do simple schedules and may more accurately reflect the human Drug-abuse situation. Much of the early work in this area used primates as subjects and focused on the behavioral variables controlling responding. It was shown that long sequences of behavior could be maintained on second-order schedules with relatively infrequent injections of Drug and that the second-order, brief-stimulus presentations were critical to the acquisition and maintenance of responding. Also, the continued presentation of the brief stimulus in extinction often led to prolonged extinction behavior. These studies clearly showed that environmental stimuli greatly influence Drug Self-Administration behavior under second-order schedules. The focus of much of the more recent work with second-order schedules has been on the evaluation of pharmacological treatments for Drug addiction, both as antagonist and substitution therapies. Both types of potential therapies have shown promise in these preclinical models of addictive behavior. The recent extension of second-order Self-Administration studies to rats as subjects has facilitated the investigation of neural mechanisms involved in this behavior. While this use of second-order schedules is a relatively recent phenomenon, significant contributions have already been made in identifying neural mechanisms critical to second-order schedule Drug Self-Administration. This active area of research holds great promise for delineating specific brain regions critical to different aspects of Drug addiction.
Leigh V. Panlilio - One of the best experts on this subject based on the ideXlab platform.
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Cocaine and selective associations : Investigations into a biological constraint on learning with Drug Self-Administration and shock avoidance as reinforcers
International Journal of Comparative Psychology, 2020Co-Authors: Stanley J. Weiss, Leigh V. Panlilio, David N. Kearns, Scott I. Cohn, Charles W. SchindlerAbstract:When a tone-light compound was a discriminative stimulus for cocaine-reinforced responding, the light gained most of the control over responding. In contrast, when the compound was an aversive SD for shock-avoidance, tone control increased. In previous studies, tone control also increased when the tone-light compound was made aversive by signaling food-absence. However, that was not the case in Experiment 2 where tone-light signaled cocaine-absence. Experiment 1 produced an interincentive (cocaine vs. shock) selective association with Drug Self-Administration maintained behavior for the first time. This extends the generality of the selective association biological constraint on learning to self-administered Drugs.
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Self‐administration of Drugs in animals and humans as a model and an investigative tool
Addiction, 2007Co-Authors: Leigh V. Panlilio, Steven R. GoldbergAbstract: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.
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Variability of Drug Self-Administration in rats.
Psychopharmacology, 2003Co-Authors: Leigh V. Panlilio, Jonathan L. Katz, Roy W. Pickens, Charles W. SchindlerAbstract: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.
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Second-order schedules of Drug Self-Administration in animals.
Psychopharmacology, 2002Co-Authors: Charles W. Schindler, Leigh V. Panlilio, Steven R. GoldbergAbstract:On a second-order schedule, a subject responds according to one schedule (the unit schedule) for a brief presentation of a stimulus such as a light. Responding by the subject on this unit schedule is then reinforced according to another schedule of reinforcement. Second-order schedules of Drug injection allow the study of more complex behavioral sequences than do simple schedules and may more accurately reflect the human Drug-abuse situation. Much of the early work in this area used primates as subjects and focused on the behavioral variables controlling responding. It was shown that long sequences of behavior could be maintained on second-order schedules with relatively infrequent injections of Drug and that the second-order, brief-stimulus presentations were critical to the acquisition and maintenance of responding. Also, the continued presentation of the brief stimulus in extinction often led to prolonged extinction behavior. These studies clearly showed that environmental stimuli greatly influence Drug Self-Administration behavior under second-order schedules. The focus of much of the more recent work with second-order schedules has been on the evaluation of pharmacological treatments for Drug addiction, both as antagonist and substitution therapies. Both types of potential therapies have shown promise in these preclinical models of addictive behavior. The recent extension of second-order Self-Administration studies to rats as subjects has facilitated the investigation of neural mechanisms involved in this behavior. While this use of second-order schedules is a relatively recent phenomenon, significant contributions have already been made in identifying neural mechanisms critical to second-order schedule Drug Self-Administration. This active area of research holds great promise for delineating specific brain regions critical to different aspects of Drug addiction.
