Influence of stress on drug-seeking behavior and addiction

pre-exposure to chronic stress on the neurotoxicity of the psychosti-mulant drug of abuse, methamphetamine. The results of our studiesindicate that prior exposure to chronic unpredictable stress augmentsthe neurotoxic effects of methamphetamine as evidenced by the long-term depletions of dopamine and/or serotonin in forebrain regionsof the rat. Moreover, the effects of chronic unpredictable stress aloneindicate a predisposition for augmented dopamine and glutamaterelease, a vulnerability to a breach of the blood–brain barrier, and adecreased expression of serotonin neurons, all ofwhich aremediated bycorticosterone and/or neuroinflammatory-dependent mechanisms.Data will be presented that indicate an additivity or synergy betweenthe effects of chronic stress and methamphetamine exposure thatculminates in the injury to neuronal and non-neuronal cells.

http://dx.doi.org/10.1016/j.ntt.2013.03.016

NBTS 14Influence of stress on drug-seeking behavior and addiction

Jerrold MeyerUniversity of Massachusetts, Amherst, MA, USA

Stress, which has been defined by Tsigos and Chrousos (2002) as“a state of disharmony or threatened homeostasis”, acutely activatesvarious central neurotransmitter pathways as well as the hypothalamic-pituitary-adrenocortical (HPA) and sympatho-adrenomedullary neu-roendocrine systems. Drug addicts frequently report that stressful lifeevents contributed to thedevelopmentof their addictionand/or to relapseto drug use during attempts at abstinence. This presentation will reviewthe literature on the role of stress in addiction and drug-seeking behavior,including both clinical and translational studies. Particular emphasis willbe placed on the involvement of stress in cocaine and alcohol dependenceand relapse, the role of glucocorticoids and the glucocorticoid receptor intheseprocesses, and interactions between theHPAaxis and thedopaminesystem. Discussion of relevant behavioral, biochemical, molecular, andneuroimaging studieswill address themechanisms underlying the abilityof stressful stimuli to increase vulnerability to drug-seeking behavior inanimals and drug addiction in humans.

Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroen-docrine factors and stress. J Psychosom Res 2002;53(4):865–71.


NBTS 15Personal memories of Pat Rodier

Richard E. ButcherSan Diego Instruments, San Diego, CA, United States

No abstract.


NBTS 16Manganese neurotoxicity: From worms to neonates

Michael Aschner, J.L. Aschner, N.L. MaitreVanderbilt, Nashville, TN, United States

Manganese is an essential mineral required for normal growth anddevelopment. Exposure to high Mn concentrations results in destructive

symmetrical lesions in thebasal ganglia, particularly in theglobuspallidus(GP), a disease referred to asmanganism; it sharesmultiple featureswithParkinson's disease (PD). Combining genetics and biochemical assays, weestablished in thenematode (Caenorhabditis elegans) that dopamine (DA)is responsible for Mn-induced DAergic neurodegeneration and that thisprocess (1) requires functional DA-reuptake transporter (DAT-1) and(2) is associatedwith oxidative stress and lifespan reduction. Additionalstudies tested whether parenteral nutrition, PN (which is routinelysupplemented with Mn) and liver disease represent risk factors forincreased Mn brain deposition in human neonates. Brain Mn wasassessed by T1 relaxation (T1R) times (using magnetic resonanceimaging; MRI) focusing on the GP. Brain Mn and its relationship to totaldietary Mn, total days on PN, conjugated bilirubin levels and blood Mnconcentrations were determined. Dietary Mn exposure was found to beinversely associatedwithGP T1R. The results establish that T1-weightedMRI can be used to screen infants on prolonged PN for increased brainMn deposition. Hepatic cholestasis was also found to represent a riskfactor for increased brain Mn deposition in neonates receiving PN.Combined our data suggest that some infants receiving prolonged PNmay be at risk for Mn neurotoxicity (Supported by R01 ES10563).


NBTS 17Cross-species comparisons of the effects of developmentalmethylmercury exposure: An update of a collaborative projectwith Dr. Patty Rodier

Thomas BurbacherUniversity of Washington, Seattle, WA, United States

The consequences of in-utero methylmercury exposure on childhealth and development remain a global concern. Maternal consump-tion of seafood contaminated with methylmercury can adversely affectthe developing nervous system resulting in a range of sensory andcognitive impairments. In 1989, the author had the pleasure ofcollaborating with Dr. Patty Rodier and Dr. Bernard Weiss on a projectaimed at comparing the effects of developmental methylmercuryexposure in humans and animals. The project was part of a workshopentitled “Qualitative and Quantitative Comparability of Human andAnimal Developmental Neurotoxicity” supported by the US Environ-mental Protection Agency. The results of this collaboration werepublished in a special issue of Neurotoxicology and Teratology in 1990.This presentation will provide an update of that collaborative project.Qualitative comparisons of specific neurotoxic end-points across specieswill be presented to demonstrate the utility of animal models forevaluating methylmercury effects at high and low doses. Quantitativecomparisons of the relationship between target organ (brain) doseand neurotoxic end-points will also be presented to evaluate the utilityof various animal models for characterizing the dose–response rela-tionship for methylmercury in humans. The approach of comparingmethylmercury effects across species based on target organ (brain) dosewas developed by Dr. Rodier and is one of her numerous outstandingcontributions to the field of neurobehavioral teratology.


NBTS 18Teratology of autism: From animal models to endophenotypes

Christopher J. Stodgella, L. Bennettob, S.L. Hymanc

aOB/GYN, University of Rochester School of Medicine, Rochester, NY,United States

NBTS 2013 Abstracts78






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Influence of stress on drug-seeking behavior and addiction