Lack of evidence for context-dependent cocaine-induced sensitization in humans: Preliminary studies

Rothman, Richard B.; Gorelick, David A.; Baumann, Michael H.; Guo, Xiao Y.; Herning, Ronald I.; Pickworth, Wallace B.; Gendron, Teri M.; Koeppl, Bonnie; Thomson, Lester E.; Henningfield, Jack E.

doi:10.1016/0091-3057(94)90073-6

Cited by 70 publications

(19 citation statements)

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“…Early studies in chronic stimulant abusers reported that these subjects developed psychosis more readily when reexposed to drug (Sato et al 1983;Satel et al 1991a, b) but more recent studies that measure sensitization (by measuring motor behaviors, vital signs, or subjective effects) have produced mixed results (Rothman et al 1994;Strakowski et al 1996;Gorelick and Rothman 1997). However, a recent PET study using the radiotracer [ 11 C]raclopride demonstrated sensitization to amphetamine in nondependent human subjects.…”

Section: Sensitization and Chronic Cocaine Exposurementioning

confidence: 93%

Imaging Neurotransmitter Release by Drugs of Abuse

Martínez

Narendran

2009

Current Topics in Behavioral Neurosciences

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Previous studies have shown that imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) radiotracers that are specific for brain dopamine receptors can be used to indirectly image the change in the levels of neurotransmitters within the brain. Most of the studies in addiction have focused on dopamine, since the dopamine neurons that project to the striatum have been shown to play a critical role in mediating addictive behavior. These imaging studies have shown that increased extracellular dopamine produced by psychostimulants can be measured with PET and SPECT. However, there are some technical issues associated with imaging changes in dopamine, and these are reviewed in this chapter. Among these are the loss of sensitivity, the time course of dopamine pulse relative to PET and SPECT imaging, and the question of affinity state of the receptor. In addition, animal studies have shown that most drugs of abuse increase extracellular dopamine in the striatum, yet not all produce a change in neurotransmitter that can be measured. As a result, imaging with a psychostimulant has become the preferred method for imaging presynaptic dopamine transmission, and this method has been used in studies of addiction. The results of these studies suggest that cocaine and alcohol addiction are associated with a loss of dopamine transmission, and a number of studies show that this loss correlates with severity of disease.

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Section: Sensitization and Chronic Cocaine Exposurementioning

confidence: 93%

Imaging Neurotransmitter Release by Drugs of Abuse

Martínez

Narendran

2009

Current Topics in Behavioral Neurosciences

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“…Rothman et al (1994) examined the effects of repeated intravenous (IV) cocaine challenges in subjects with a recent history of IV cocaine use. They observed no progression in response to repeated cocaine exposure among these subjects.…”

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confidence: 99%

Human Response to Repeated Low-Dose d-Amphetamine: Evidence for Behavioral Enhancement and Tolerance

Strakowski

2001

Neuropsychopharmacology

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Previously, we reported progressively greater behavioral responses to repeated d-amphetamine in human subjectsBehavioral sensitization is a progressively greater and enduring behavioral response that occurs following repeated stimulant administration. This phenomenon has been widely studied in animals and has been hypothesized to underlie aspects of human stimulant addiction, as well as several psychiatric syndromes (Robinson and Becker 1986;Robinson and Berridge 1993). Despite the potential importance of behavioral sensitization in human clinical conditions, few controlled human studies of this process have been reported.During the past several years, we have investigated whether repeated low-dose d-amphetamine leads to a progressive behavioral response when administered to human volunteers, consistent with a behavioral sensitization model. In the first 4-day study, 11 healthy subjects were given two oral doses of d-amphetamine (0.25 mg/kg) at 48-hour intervals alternating with two similarly spaced, matched placebo doses (Strakowski et al. 1996). Subjects exhibited significantly greater eye blink rates and changes in energy level, mood, and talkativeness following the second d-amphetamine dose as compared to the first amphetamine and both placebo doses. In a separate study of 11 different healthy subjects, three oral doses of d-amphetamine (0.25 mg/kg) were administered at 48-hour intervals again alternating

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“…Regardless of the findings that cocaine selfadministration prolonged over days can result in either elevated responses due to cocaineinduced enhanced locomotion or decreased responses due to acute tolerance-like effects, intermittent exposure to cocaine during self-administration over multiple days regardless of session length, results in an increase in reinforcement potential [117] and cocaine sensitization [106]. Unfortunately, there has been a noticeable dearth of studies specifically examining this facet of the addiction process in drug addicts [14], although a limited studies in non-drug users injected with amphetamine over 4 days report an increase in spontaneous blink rate and euphoria [15,16].…”

Section: Introductionmentioning

confidence: 99%

Section: Cocaine Addiction and Sensitizationmentioning

confidence: 99%

“…In fact, the Incans also reported that the effects of cocaine increase over days of use, a phenomena that researchers at the time described as "increase in reflex excitability" paired with increased "gayness" [13]. Sensitization, by the nature of the phenomenon, is practically impossible to observe in human addicts, and has long been a topic on controversy among researchers of addiction [14].The crux of the argument against cocaine sensitization stems from the difficulty of observing its development in humans. Direct observation is virtually impossible since it would occur very early in the addiction process before addicts would usually seek professional help to control their addiction.…”

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confidence: 99%

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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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Lack of evidence for context-dependent cocaine-induced sensitization in humans: Preliminary studies

Cited by 70 publications

References 24 publications

Imaging Neurotransmitter Release by Drugs of Abuse

Imaging Neurotransmitter Release by Drugs of Abuse

Human Response to Repeated Low-Dose d-Amphetamine: Evidence for Behavioral Enhancement and Tolerance

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

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