Dopamine antagonist and 'binge' cocaine effects on rat opioid and dopamine transporter mRNAs

Spangler, Rudolph; Zhou, Yan; Maggos, Christopher E.; Злобин, А Н; Ho, Ann; Kreek, Mary Jeanne

doi:10.1097/00001756-199609020-00028

Cited by 54 publications

(28 citation statements)

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“…Altered expression of the prodynorphin gene in the central nervous system has been observed in several experimental models of psychiatric diseases, including drug abuse. Our laboratory and others have consistently found that mRNA levels of dynorphin in the brains of rats are elevated following a single injection of cocaine [Hurd et al, 1992], cocaine self-administration [Hurd et al, 1992;Daunais et al, 1993], and acute or chronic ''binge'' cocaine administration [Spangler et al, 1993[Spangler et al, , 1996. In addition, opioid peptides are important neuromodulators that are directly and indirectly associated with the reward pathways in the brain.…”

Section: Introductionmentioning

confidence: 94%

Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse

Chen

LaForge

et al. 2002

Am. J. Med. Genet.

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It has been demonstrated that the opioid peptide dynorphin plays a role in modulating responses to several psychoactive substances including cocaine. Our laboratory and others have found that mRNA levels of dynorphin in the caudate and putamen are elevated after acute or chronic cocaine exposure in rats. Recently, a 68‐base pair (bp) repeat polymorphism within the core promoter region of the human prodynorphin gene has been reported to occur in alleles containing one, two, three, or four copies. This repeat contains a putative AP‐1 transcription factor binding site; reporter gene constructs with three or four, but not one or two, copies of the tandem repeats were shown to be associated with increases in transcriptional activation in in vitro cellular assays. We hypothesize that this polymorphism may be associated with individual differences in vulnerability to cocaine dependence or abuse. From an ongoing study of the genetics of addiction, 174 subjects were studied, including individuals with a primary diagnosis (DSM‐IV criteria) of cocaine dependence (N = 61) or abuse (N = 22), and controls with no history of any substance dependence or abuse (N = 91). We designed primers for polymerase chain reaction (PCR) to amplify sequences of the promoter region of the prodynorphin gene containing the repeat element. The association of alleles containing three or four repeats with cocaine dependence/abuse was examined. With data stratified by ethnic group, pooled relative risk (RR) with Mantel‐Haenszel Chi square was calculated: RR = 0.59 (95% confidence interval 0.37–0.95), χ2(1) = 4.14, P = 0.042. Our results suggest that this allelic variation at the promoter region of the prodynorphin gene (alleles with three or four repeats), which may result in enhanced transcription of the gene, may contribute to relative protection and decrease individual vulnerability to develop cocaine dependence or abuse. © 2002 Wiley‐Liss, Inc.

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Section: Introductionmentioning

confidence: 94%

Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse

Chen

LaForge

et al. 2002

Am. J. Med. Genet.

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“…In addition, binge cocaine administration increased preproenkephalin and preprodynorphin mRNA in the striatum (Daunais et al, 1993(Daunais et al, , 1995Spangler et al, 1996;Hurd et al, 1992) and cocaine administration increased m-opioid receptor mRNA in the NAc (Azaryan et al, 1996). Opioid receptors may be involved in cocaine craving since m-opioid receptor binding measured with positron emission tomography in the brains of cocaine addicts after 1-4 days of withdrawal was increased and positively correlated with the severity of cocaine craving (Zubieta et al, 1996).…”

Section: Potential Mechanismsmentioning

confidence: 99%

Self-Administered Heroin and Cocaine Combinations in the Rat: Additive Reinforcing Effects—Supra-Additive Effects on Nucleus Accumbens Extracellular Dopamine

Smith

Coller

et al. 2005

Neuropsychopharmacol

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The concurrent use of cocaine and opiate combinations (speedball) has increased since the 1970s and now represents a growing subset of intravenous drug abusers. An isobolographic analysis was applied to the ascending limb of the dose-effect curves for rat selfadministration of cocaine, heroin, and their combination to determine the nature of the interaction. The addition of heroin to cocaine shifted the dose-effect curve for self-administration to the left, and the modulation in reinforcing efficacy of the combination of cocaine and heroin was found to be additive. A second experiment used microdialysis to determine the effects of this drug combination on nucleus accumbens (NAc) extracellular levels of dopamine ([DA] e ) in rats self-administering low doses of cocaine, heroin, or cocaine/ heroin combinations. These doses of cocaine and cocaine/heroin combinations significantly increased NAc [DA] e , while heroin alone did not. The ratio of the % baseline of [DA] e (or the dialysate concentrations of DA) to cocaine in the dialysate was higher during selfadministration of cocaine/heroin combinations than with cocaine alone. These data indicate that although the interaction between cocaine and heroin in maintaining self-administration is additive, a potentiation of NAc dopaminergic neurotransmission is present, suggesting that NAc [DA] e may not be a direct measure of reinforcing efficacy and/or it is not central to the mediation of the selfadministration of this drug combination.

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“…As with the DAT binding studies, the dose of cocaine appears to be important, with 10 mg/kg daily for ten days producing no change, but 15 or 25 mg/kg daily leading to decreases in DAT mRNA in substantia nigra and ventral tegmental area 1 h later (Letchworth et al, 1997) and in the parabrachial pigmentosis 4 h after the last injection (Burchett and Bannon, 1997). When tested ten days later, however, there were no significant changes (Spangler et al, 1996;Maggos et al, 1997). In human brain, it has been reported that cocaine produced no change in DAT mRNA in substantia nigra (Chen et al, 1999).…”

Section: Introductionmentioning

confidence: 95%

The role of the dopamine transporter in cocaine abuse

Izenwasser

2004

neurotox res

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There have been many studies aimed at understanding the role that the dopamine transporter plays in cocaine abuse. Most studies suggest that inhibition of dopamine uptake by cocaine is the primary mechanism by which its behavioral effects are produced. Because of the strong relationship between binding to the dopamine transporter and the behavioral effects of cocaine, the dopamine transporter has on occasion been referred to as the cocaine binding site. Chronic studies using cocaine or selective inhibitors of dopamine, norepinephrine, or serotonin uptake suggest that while a selective dopamine uptake inhibitor can produce sensitization to cocaine, the long-lasting sensitized response to a cocaine challenge observed in cocaine-pretreated rats is due to cocaine's action on a system other than, or in addition to, dopamine. Thus, while dopamine appears to be important for the behavioral effects of cocaine, it appears that neurochemical systems other than dopamine likely play a role in the behavioral effects of chronic cocaine.

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Dopamine antagonist and 'binge' cocaine effects on rat opioid and dopamine transporter mRNAs

Cited by 54 publications

References 0 publications

Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse

Potentially functional polymorphism in the promoter region of prodynorphin gene may be associated with protection against cocaine dependence or abuse

Self-Administered Heroin and Cocaine Combinations in the Rat: Additive Reinforcing Effects—Supra-Additive Effects on Nucleus Accumbens Extracellular Dopamine

The role of the dopamine transporter in cocaine abuse

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