Dopamine transporter down‐regulation following repeated cocaine: implications for 3,4‐methylenedioxymethamphetamine‐induced acute effects and long‐term neurotoxicity in mice

Peraile, Ines; Torres, Elisa; Mayado, Andrea; Izco, María; López-Jiménez, Alejandro; López-Moreno, J. A.; Colado, M. Isabel; O’Shea, Esther

doi:10.1111/j.1476-5381.2009.00522.x

Cited by 18 publications

(13 citation statements)

References 69 publications

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“…The molecular targets are often drug specific, for example, the dopamine transporter for cocaine and amphetamine exposure (Calipari, Ferris, Salahpour, Caron, & Jones, 2013; Peraile et al, 2010), opioid receptors and propeptide genes for opioid exposure (Diaz, Barros, Antonelli, Rubio, & Balerio, 2006), and GABA and glutamate receptors for other drug and alcohol exposure (Enoch et al, 2012; Meinhardt et al, 2013; Nona, Li, & Nobrega, 2013; Schumann & Yaka, 2009; Swanson, Baker, Carson, Worley, & Kalivas, 2001; Zhang et al, 2009; Zhou et al, 2013). Certain aspects of cell signaling, early transcriptional response, and learning have been obvious, and fruitful, targets for study in the addictions.…”

Section: Molecular Adaptations Accompanying Early Response and Lonmentioning

confidence: 99%

Gene Expression in the Addicted Brain

Zhou¹,

Enoch²,

Goldman³

2014

International Review of Neurobiology

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Addiction is due to changes in the structure and function of the brain, including neuronal networks and the cells that comprise them. Within cells, gene expression changes can track and help explain their altered function. Transcriptional changes induced by addictive agents are dynamic and divergent and range from signal pathway-specific perturbations to widespread molecular and cellular dysregulation that can be measured by “omic” methods and that can be used to identify new pathways. The molecular effects of addiction depend on timing of exposure or withdrawal, the stage of adaptation, the brain region, and the behavioral model, there being many models of addiction. However, the molecular neural adaptations across different drug exposures, conditions, and regions are to some extent shared and can reflect common actions on pathways relevant to addiction. Epigenetic studies of DNA methylation and histone modifications and studies of regulatory RNA networks have been informative for elucidating the mechanisms of transcriptional change in the addicted brain.

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Section: Molecular Adaptations Accompanying Early Response and Lonmentioning

confidence: 99%

Gene Expression in the Addicted Brain

Zhou¹,

Enoch²,

Goldman³

2014

International Review of Neurobiology

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“…In addition to the acute pharmacological effects of cocaine, chronic administration has been shown to modify presynaptic DA terminal function. For example, D2-type DA autoreceptor numbers and activity, tyrosine hydroxylase (TH) levels, DAT cell surface expression, and maximal rates of DA uptake (V max ) are all changed by chronic or repeated cocaine exposure (Daws et al, 2002;Collins and Izenwasser, 2002;Self et al, 2004;Peraile et al, 2010). The direction and magnitude of these changes, DA uptake in particular, appear contingent upon time course, withdrawal period, and route of cocaine administration, among other factors (Ramamoorthy et al, 2010;Peraile et al, 2010;Mandt and Zahniser, 2010).…”

Section: Introductionmentioning

confidence: 99%

Cocaine Self-Administration Produces Pharmacodynamic Tolerance: Differential Effects on the Potency of Dopamine Transporter Blockers, Releasers, and Methylphenidate

Ferris

Calipari

Mateo

et al. 2012

Neuropsychopharmacol

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The dopamine transporter (DAT) is the primary site of action for psychostimulant drugs such as cocaine, methylphenidate, and amphetamine. Our previous work demonstrated a reduced ability of cocaine to inhibit the DAT following high-dose cocaine selfadministration (SA), corresponding to a reduced ability of cocaine to increase extracellular dopamine. However, this effect had only been demonstrated for cocaine. Thus, the current investigations sought to understand the extent to which cocaine SA (1.5 mg/kg/inf Â 40 inf/ day Â 5 days) altered the ability of different dopamine uptake blockers and releasers to inhibit dopamine uptake, measured using fastscan cyclic voltammetry in rat brain slices. We demonstrated that, similar to cocaine, the DAT blockers nomifensine and bupropion were less effective at inhibiting dopamine uptake following cocaine SA. The potencies of amphetamine-like dopamine releasers such as 3,4-methylenedioxymethamphetamine, methamphetamine, amphetamine, and phentermine, as well as a non-amphetamine releaser, 4-benzylpiperidine, were all unaffected. Finally, methylphenidate, which blocks dopamine uptake like cocaine while being structurally similar to amphetamine, shared characteristics of both, resembling an uptake blocker at low concentrations and a releaser at high concentrations. Combined, these experiments demonstrate that after high-dose cocaine SA, there is cross-tolerance of the DAT to other uptake blockers, but not releasers. The reduced ability of psychostimulants to inhibit dopamine uptake following cocaine SA appears to be contingent upon their functional interaction with the DAT as a pure blocker or releaser rather than their structural similarity to cocaine. Further, methylphenidate's interaction with the DAT is unique and concentration-dependent.

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“…1 It is also evident that chronic abuse of psychostimulants (such as methamphetamine (METH) and cocaine) causes significant level of neurotoxicity and inflammation leading to persistent neurochemical abnormalities and loss of synaptic integrity. [2][3][4][5] Pronounced levels of oxidative stress and mitochondrial dysfunction, due to uncontrolled increase in cellular reactive oxygen (ROS) and nitrogen species (RNS), were identified as major pathological mechanisms underlying psychostimulant or smoking-induced neurodegeneration. [6][7][8][9][10][11][12] In fact, clinical studies suggest a diminished anti-oxidative stress response in cocaine or methamphetamine abusers compared with normal subjects.…”

Section: Introductionmentioning

confidence: 99%

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

Sajja

Rahman

Cucullo

2015

J Cereb Blood Flow Metab

117

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Psychostimulants and nicotine are the most widely abused drugs with a detrimental impact on public health globally. While the long-term neurobehavioral deficits and synaptic perturbations are well documented with chronic use of methamphetamine, cocaine, and nicotine, emerging human and experimental studies also suggest an increasing incidence of neurovascular complications associated with drug abuse. Short-or long-term administration of psychostimulants or nicotine is known to disrupt blood-brain barrier (BBB) integrity/function, thus leading to an increased risk of brain edema and neuroinflammation. Various pathophysiological mechanisms have been proposed to underlie drug abuse-induced BBB dysfunction suggesting a central and unifying role for oxidative stress in BBB endothelium and perivascular cells. This review discusses drug-specific effects of methamphetamine, cocaine, and tobacco smoking on brain microvascular crisis and provides critical assessment of oxidative stress-dependent molecular pathways focal to the global compromise of BBB. Additionally, given the increased risk of human immunodeficiency virus (HIV) encephalitis in drug abusers, we have summarized the synergistic pathological impact of psychostimulants and HIV infection on BBB integrity with an emphasis on unifying role of endothelial oxidative stress. This mechanistic framework would guide further investigations on specific molecular pathways to accelerate therapeutic approaches for the prevention of neurovascular deficits by drugs of abuse.

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Dopamine transporter down‐regulation following repeated cocaine: implications for 3,4‐methylenedioxymethamphetamine‐induced acute effects and long‐term neurotoxicity in mice

Cited by 18 publications

References 69 publications

Gene Expression in the Addicted Brain

Gene Expression in the Addicted Brain

Cocaine Self-Administration Produces Pharmacodynamic Tolerance: Differential Effects on the Potency of Dopamine Transporter Blockers, Releasers, and Methylphenidate

Drugs of abuse and blood-brain barrier endothelial dysfunction: A focus on the role of oxidative stress

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