Cocaine reinforced progressive ratio performance in the rhesus monkey

Bedford, John A.; Bailey, Lillian P.; Wilson, Marvin C.

doi:10.1016/0091-3057(78)90214-9

Cited by 60 publications

(21 citation statements)

References 10 publications

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“…Responding has been reported to increase only (Hodos 1961), to increase to an asymptote (Griffiths et al 1975;Depoortere et al 1993;Roberts 1993) and to increase to a maximum and then decrease (Griffiths et al 1979a;Winger and Woods 1985). Additionally, all possible outcomes have been reported to occur across subjects (Griffths et al 1978;Risner and Silcox 1981;Bedford et al 1978). In the present experiment, responding maintained by both drugs at the 30-min ITI was, in fact, asymptotic, though responding may have decreased at the 0.4 mg/kg per injection dose of cocaine had all monkeys been tested.…”

Section: Discussionmentioning

confidence: 60%

“…Yanagita (1973) first suggested that PR procedures could be used to measure the reinforcing efficacy of drugs. Since that time, it has been established that, as with non-drug reinforcers, BP increases to a maximum with reinforcer magnitude (dose) for psychomotor stimulants in non-human primates (Bedford et al 1978;Griffiths et al 1978;Winger and Woods 1985), rats (Depoortere et al 1993;Roberts 1993;Roberts et al 1989) and dogs (Risner and Silcox 1981). Although less information is available, this general conclusion seems to hold for opioids (Hoffmeister 1979;Mello et al 1988;Roberts and Bennett 1993) and CNS depressants (Winger 1993) as well.…”

Section: Introductionmentioning

confidence: 97%

“…The response requirement at which responding ceases has been called the breaking point or breakpoint (BP). A variety of PR schedules have been used to study behavior maintained by several different positive reinforcers, including food (Spear and Katz 1991), sweetened solutions (Bedford et al 1978;Hodos 1961) and electrical stimulation of the brain (Hodos 1965;Keesey and Goldstein 1968). A general conclusion of those studies has been that BP increases with reinforcer magnitude.…”

Section: Introductionmentioning

confidence: 98%

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Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys responding under a progressive-ratio schedule

Woolverton

1995

Psychopharmacology

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Rhesus monkeys (n = 5) were prepared with chronic IV catheters and trained to lever press under a PR schedule of drug injection. The schedule consisted of five components, each made up of four trials (i.e., 20 trials total). Each trial within a component had the same response requirement. The response requirement in the first component was 120/trial and doubled in successive components to a maximum of 1920 in the fifth. A trial ended with an injection or the expiration of a 12-min limited hold (LH). The inter-trial interval (ITI) was 15 or 30 min. Following an injection or expiration of the LH, all stimulus lights were extinguished and responding had no consequence for the remainder of the trial. A session ended when either all 20 injections were self-administered or the response requirement was not met within the LH for two consecutive trials. The number of injections/session and responses/session increased with dose for cocaine (0.012-0.1 mg/kg per injection) and procaine (0.12-2.0 mg/kg per injection) at both ITI values. At the 15-min ITI, responding decreased again at higher doses in some monkeys with cocaine and in all monkeys with procaine. At maximum, cocaine maintained significantly more injections and responses/session when the ITI was 30 min than when it was 15 min. In contrast, the increase in ITI did not increase the maximum maintained by procaine. Cocaine was approximately 10-fold more potent than procaine and maintained at maximum significantly more injections and responses than procaine when ITI was 30 min but not when the ITI was 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 98%

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Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys responding under a progressive-ratio schedule

Woolverton

1995

Psychopharmacology

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“…In the first implementation of the PR schedule for drug selfadministration in rats , the response requirements were increased after the delivery of each reinforcement (i.e. within a session) as originally suggested by Hodos (1961) and later adapted by Bedford (1978) for studies in rhesus monkeys. This procedure yields a daily assessment of breakpoint.…”

Section: Changes In the Motivation To Self-administer Cocainementioning

confidence: 99%

How to make a rat addicted to cocaine

Roberts

Morgan

Liu

2007

Progress in Neuro-Psychopharmacology and Biological Psychiatry

123

115

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Procedures have been developed which provide extremely stable patterns of cocaine selfadministration in rats and these have been useful in lesion and drug pretreatment studies aimed at understanding the neurobiology of cocaine reinforcement. The issue now is whether studying the neurobiology of reinforcement is the same as studying the neurobiology of addiction. If the goal is to understand a progressive and deteriorating disorder, then the self-administration procedures should model specific aspects of the progressive stages of the addiction process. Here we review theoretical strategies for modeling the addiction process and present data from a series of experiments from our laboratory showing conditions which produce a progressive change in the motivation to selfadminister cocaine in rats. This phenomenon is revealed by an escalation in breakpoints on a progressive ratio schedule. The effect, which is robust and persistent, depends on dose and speed of injection. Interestingly, high drug intake can retard the development of this effect, which we argue indicates that the addiction process has a developmental sequence. Finally, we suggest that specific parameters (dose, price and availability) can be used to examine the transition from recreational use to binge-like intake.

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“…In comparison, increasing the labor cost associated with drug infusions through the inclusion of a progressive ratio (PR) schedule has the ability to increase the reinforcement strength of cocaine self-administration (termed salience) by requiring seemingly random, ever-increasing effort to acquire subsequent doses of drug until a breakpoint is reached. At this breakpoint, the animal is unwilling to continue responding for the next dose, or cannot reach criteria in the allotted time [110,111]. To accomplish this, PR testing uses a specific formula to generate the number of responses needed to achieve the next dose and increases in a dynamic fashion, in contrast to a discrete number of responses under FR [111].…”

Section: Introductionmentioning

confidence: 99%

Effects of Cocaine Sensitization on Drug Self-Administration, Mesocorticolimbic SAPAP Levels, and Prefrontal Ionotropic Glutamate Receptors

Summers¹

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DEDICATIONTo my mother Andrea, who through her example taught me that the values of hard work, integrity, and good manners never go out of style To Karen, who taught me the true meaning of courage under the threat of certain death, and that those no longer with us physically continue to live in our thoughts iv ACKNOWLEDGEMENTS All information and data in this text was only possible due to the generous support and inexhaustible patience of my advisor Jeff Steketee and my graduate committee (which included Drs. John Boughter, Michael McDonald, Kazuko Sakata, and Wen Lin Sun). Also, instrumental to the completion of this project were the helping hands of Dr. Steve Tavalin. This project also could have never been completed without financial support from the University of Tennessee Health Science Center Neuroscience Institute and the National Institute on Drug Abuse (NIDA).v ABSTRACT Towards the goal of improving the knowledge base of how drugs of abuse function to create addicts and using currently uninvestigated areas of this knowledge base, we focused our research studies the male albino rat, and strived to explain how cocaine sensitization alters particular molecular mechanisms in the mesocorticolimbic system related to glutamate receptors, SAPAPs, and affects drug self-administration. Taking all the previously discussed research studies into consideration, we hypothesized that low-dose cocaine self-administration would yield a significant elevation in drug seeking behavior for psychostimulant sensitized animals. For specific changes at the PSD, we hypothesized that acute cocaine exposure and/or cocaine sensitization would alter iGluRs levels in the mPFC, and SAPAP levels in multiple sites of the mesocorticolimbic system. To test these hypotheses, we investigated the effects of psychostimulant sensitization on various parameters of self-administration by infusing a low-dose cocaine reward proven to not induce sensitization during self-administration (reported here as 0.3 mg/kg/infusion). Although drug exposure did not significantly alter self-administration behavior, we did find that more drug exposed subjects acquired selfadministration behavior when compared to drug naïve controls. We also investigated the effects of acute cocaine exposure and/or cocaine sensitization on iGluRs in the mPFC and SAPAPs in the entire mesocorticolimbic circuit thru western blotting, immunolabeling of proteins of interest, and comparing protein levels to those found in cocaine naïve controls. A limited self-administration protocol also tested if SAPAP levels were altered by self-administration of a low-dose cocaine reward. For these experiments, we found that SAPAP protein levels are altered in multiple regions of the mesocorticolimbic system in response to contingent and non-contingent cocaine exposure, and that iGluR receptor subunits are altered in the prefrontal cortex in response to non-contingent cocaine exposure. vi PREFACEThe Incans that first cultivated the coca plant for medicinal use five millennia ago reserved this "Elix...

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Cocaine reinforced progressive ratio performance in the rhesus monkey

Cited by 60 publications

References 10 publications

Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys responding under a progressive-ratio schedule

Comparison of the reinforcing efficacy of cocaine and procaine in rhesus monkeys responding under a progressive-ratio schedule

How to make a rat addicted to cocaine

Effects of Cocaine Sensitization on Drug Self-Administration, Mesocorticolimbic SAPAP Levels, and Prefrontal Ionotropic Glutamate Receptors

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