The self-administration of rapidly delivered cocaine promotes increased motivation to take the drug: contributions of prior levels of operant responding and cocaine intake

Bouayad-Gervais, Karim; Minogianis, Ellie-Anna; Lévesque, Daniel; Samaha, Anne‐Noël

doi:10.1007/s00213-014-3576-4

Cited by 19 publications

(21 citation statements)

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“…Finally, when the speed of i.v. drug injection is varied during LgA sessions, rats allowed to self-administer rapid cocaine injections (5 versus 90 s) subsequently show increased motivation to obtain the drug (Bouayad-Gervais et al, 2014 andMinogianis et al, 2013). This effect is illustrated in Fig.…”

Section: The Long-access Modelmentioning

confidence: 91%

“…This prompted us and others to ask whether the speed of drug delivery plays a role in the propensity to escalate drug consumption. Work on this issue showed that when daily access to cocaine is increased from 1 to 6 h, rats given access to rapid (5-45 s) versus slower (90 s) injections of cocaine take more drug and are also more likely to escalate their consumption over days (Bouayad-Gervais et al, 2014, Minogianis et al, 2013and Wakabayashi et al, 2010. Fig.…”

Section: Bmentioning

confidence: 99%

“…For instance, compared to rats given limited daily access to cocaine, rats given LgA sessions are more vulnerable to drugprimed reinstatement of previously extinguished responding for cocaine (Ahmed and Cador, 2006, Ahmed and Koob, 1998, Knackstedt and Kalivas, 2007and Mantsch et al, 2004. LgA rats also show greater responding for cocaine in spite of punishment (footshock) (Vanderschuren and Everitt, 2004), and also reach higher breakpoints for cocaine under progressive ratio conditions (Hao et al, 2010, Paterson and Markou, 2003and Wee et al, 2008; note however that this latter effect is not always observed, Bouayad-Gervais et al, 2014, Liu et al, 2005aand Oleson and Roberts, 2009). …”

Section: The Long-access Modelmentioning

confidence: 99%

“…The ability of rapidly administered cocaine to increase motivation to obtain drug and the susceptibility to reinstatement is not just a consequence of the amount of drug previously consumed. Even when the rats self-administering rapid cocaine injections take the same amount as rats self-administering slower injections, the former show greater motivation for drug and a more persistent vulnerability to reinstatement (Bouayad-Gervais et al, 2014, Minogianis et al, 2013and Wakabayashi et al, 2010. Thus, how much, how often and how fast a drug reaches the brain all determine the neuroplasticity that underlies changes in appetitive behaviours characteristic of addiction.…”

Section: The Long-access Modelmentioning

confidence: 99%

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How fast and how often: The pharmacokinetics of drug use are decisive in addiction

Allain

Minogianis

Roberts

et al. 2015

Neuroscience & Biobehavioral Reviews

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169

120

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How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, 'spiking' brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.

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Section: The Long-access Modelmentioning

confidence: 91%

Section: Bmentioning

confidence: 99%

Section: The Long-access Modelmentioning

confidence: 99%

Section: The Long-access Modelmentioning

confidence: 99%

See 2 more Smart Citations

How fast and how often: The pharmacokinetics of drug use are decisive in addiction

Allain

Minogianis

Roberts

et al. 2015

Neuroscience & Biobehavioral Reviews

Self Cite

169

120

View full text Add to dashboard Cite

show abstract

“…administration experiments were based on used faster pumps that delivered 1.6 ml/minute [95], compared to ours that infuse drug at approximately 1.0 ml/minute. The relatively slow speed of the self-administration pumps could have lowered the efficacy of the cocaine delivery system, as faster speeds of delivery results in increased motivation during self-administration in rats [120,121] and humans [122,123]. This explains why all routes of cocaine absorption used by humans facilitate concentrated, rapid delivery of concentrated drug doses into the bloodstream [124,125].…”

Section: Discussionmentioning

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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Drug Self-Administration as a Model to Study the Reward System

Allain

Samaha

2020

Neuromethods

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The self-administration of rapidly delivered cocaine promotes increased motivation to take the drug: contributions of prior levels of operant responding and cocaine intake

Cited by 19 publications

References 76 publications

How fast and how often: The pharmacokinetics of drug use are decisive in addiction

How fast and how often: The pharmacokinetics of drug use are decisive in addiction

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

Drug Self-Administration as a Model to Study the Reward System

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