Medicine and Health Sciences Commons^™

Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects Of Cocaine, Aric Madayag, Doug Lobner, Kristen S. Kau, John R. Mantsch, Omer Abdulhameed, Matthew Hearing, Mark D. Grier, David A. Baker

Biomedical Sciences Faculty Research and Publications

Cocaine produces a persistent reduction in cystine–glutamate exchange via system x_c− in the nucleus accumbens that may contribute to pathological glutamate signaling linked to addiction. System x_c− influences glutamate neurotransmission by maintaining basal, extracellular glutamate in the nucleus accumbens, which, in turn, shapes synaptic activity by stimulating group II metabotropic glutamate autoreceptors. In the present study, we tested the hypothesis that a long-term reduction in system x_c− activity is part of the plasticity produced by repeated cocaine that results in the establishment of compulsive drug seeking. To test this, the cysteine prodrug N-acetylcysteine …

Augmented Hypothalamic Corticotrophin-Releasing Hormone Mrna And Corticosterone Responses To Stress In Adult Rats Exposed To Perinatal Hypoxia, Hershel Raff, Lauren Jacobson, William E. Cullinan

Biomedical Sciences Faculty Research and Publications

Stressful events before or just after parturition alter the subsequent phenotypical response to stress in a general process termed programming. Hypoxia during the period before and during parturition, and in the postnatal period, is one of the most common causes of perinatal distress, morbidity, and mortality. We have found that perinatal hypoxia (prenatal day 19 to postnatal day 14) augmented the corticosterone response to stress and increased basal corticotrophin-releasing hormone (CRH) mRNA levels in the parvocellular portion of the paraventricular nucleus (PVN) in 6-month-old rats. There was no effect on the levels of hypothalamic parvocellular PVN vasopressin mRNA, anterior pituitary …

Mutations At F637 In The Nmda Receptor Nr2a Subunit M3 Domain Influence Agonist Potency, Ion Channel Gating And Alcohol Action, H. Ren, Ak Salous, J. M. Paul, Rh Lipsky, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

Background and purpose:

NMDA receptors are important molecular targets of ethanol action in the CNS. Previous studies have identified a site in membrane-associated domain 3 (M3) of the NR1 subunit and two sites in M4 of the NR2A subunit that influence alcohol action; the sites in NR2A M4 also regulate ion channel gating. The purpose of this study was to determine whether mutations at the site in the NR2A subunit corresponding to the NR1 M3 site influence alcohol action and ion channel gating.

Experimental approach:

We investigated the effects of mutations at phenylalanine (F) 637 of the NR2A subunit using …

Restraint-Induced Corticosterone Secretion And Hypothalamic Crh Mrna Expression Are Augmented During Acute Withdrawal From Chronic Cocaine Administration, John R. Mantsch, Sarah Taves, Tayyiba Khan, Eric S. Katz, Tanveer Sajan, Lee C. Tang, William E. Cullinan, Dana R. Ziegler

Biomedical Sciences Faculty Research and Publications

Stress responses during cocaine withdrawal likely contribute to drug relapse and may be intensified as a consequence of prior cocaine use. The present study examined changes in stressor-induced activation of the hypothalamic–pituitary–adrenal (HPA) axis during acute withdrawal from chronic cocaine administration. Adult male Sprague–Dawley rats received daily administration of cocaine (30 mg/kg, i.p.) or saline for 14 days. Twenty-four hours after the last injection, rats in each group were sacrificed under stress-free conditions or following 30 min of immobilization. Plasma corticosterone (CORT) was measured in trunk-blood using radioimmunoassay, corticotropin-releasing hormone (CRH) mRNA levels in the paraventricularnucleus (PVN) of the hypothalamus …

Β-N-Methylamino-L-Alanine Enhances Neurotoxicity Through Multiple Mechanisms, Doug Lobner, Peachy Mae T. Piana, Abed K. Salous, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The idea that the environmental toxin β-N-methylamino-l-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer's patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 μM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and …