Medicine and Health Sciences Commons^™

A Single Phenylalanine Residue In The Main Intracellular Loop Of Α1 Γ-Aminobutyric Acid Type A And Glycine Receptors Influences Their Sensitivity To Propofol, Gustavo Moraga-Cid, Gonzalo E. Yevenes, Günther Schmalzing, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

Background: The intravenous anesthetic propofol acts as a positive allosteric modulator of glycine (GlyRs) and γ-aminobutyric acid type A (GABA_ARs) receptors. Although the role of transmembrane residues is recognized, little is known about the involvement of other regions in the modulatory effects of propofol. Therefore, the influence of the large intracellular loop in propofol sensitivity of both receptors was explored. Methods: The large intracellular loop of α₁ GlyRs and α₁β₂ GABA_ARs was screened using alanine replacement. Sensitivity to propofol was studied using patch-clamp recording in HEK293 cells transiently transfected with …

Augmented Cocaine Seeking In Response To Stress Or Crf Delivered Into The Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated By Crf Receptor Type 1 But Not Crf Receptor Type 2, Jordan M. Blacktop, Chad Seubert, David A. Baker, Nathan Ferda, Geng Lee, Evan N. Graf, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

Stressful events are determinants of relapse in recovering cocaine addicts. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) regulation of neurocircuitry involved in drug seeking. We previously reported that the reinstatement of cocaine seeking by a stressor (footshock) is CRF dependent and is augmented in rats that self-administered cocaine under long-access (LgA; 6 h daily) conditions for 14 d when compared with rats provided shorter daily cocaine access [short access (ShA) rats; 2 h daily]. Further, we have demonstrated that reinstatement in response to intracerebroventricular CRF administration is heightened in LgA rats. …

Natural And Synthetic Corticosteroids Inhibit Uptake2-Mediated Transport In Cns Neurons, Jonathan E. Hill, Khadijah Makky, Lalita Shrestha, Cecilia J. Hillard, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

In addition to exerting actions via mineralocorticoid and glucocorticoid receptors, corticosteroids also act by inhibiting uptake₂, a high-capacity monoamine transport system originally described in peripheral tissues. Recent studies have demonstrated that uptake₂ transporters are expressed in the brain and play roles in monoamine clearance, suggesting that they mediate some corticosteroid effects on physiological and behavioral processes. However, the sensitivity of brain uptake₂ to many natural and synthetic corticosteroids has not been characterized. Cultured rat cerebellar granule neurons (CGNs) were previously shown to exhibit corticosterone-sensitive accumulation of the uptake₂ substrate1-methyl-4-phenylpyridinium (MPP⁺). We examined the …

Oral Administration Of Levo-Tetrahydropalmatine Attenuates Reinstatement Of Extinguished Cocaine Seeking By Cocaine, Stress Or Drug-Associated Cues In Rats, Yazmin Figueroa-Guzman, Christopher R. Mueller, Oliver Vranjkovic, Samantha Wisniewski, Zheng Yang, Shi-Jiang Li, Colin Bohr, Evan N. Graf, David A. Baker, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, …

Insulin-Like Growth Factor 1 And Transforming Growth Factor-Β Stimulate Cystine/Glutamate Exchange Activity In Dental Pulp Cells, Katherine Pauly, Kymberly Fritz, Alyssa Furey, Doug Lobner

Biomedical Sciences Faculty Research and Publications

Introduction

The growth factors insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) are protective to dental pulp cells in culture against the toxicity of the composite materials Durafill VS and Flow Line (Henry Schein Inc, New York, NY). Because the toxicity of these materials is mediated by oxidative stress, it seemed possible that the protective effects of IGF-1 and TGF-β were through the enhancement of an endogenous antioxidant mechanism.

Methods

We used cultured dental pulp cells to determine the mechanism of the protective effects of IGF-1 and TGF-β, focusing on the glutathione system and the role of cystine/glutamate exchange …

Forebrain Origins Of Glutamatergic Innervation To The Rat Paraventricular Nucleus Of The Hypothalamus: Differential Inputs To The Anterior Versus Posterior Subregions, Yvonne M. Ulrich-Lai, Kenneth R. Jones, Dana R. Ziegler, William E. Cullinan, James P. Herman

Biomedical Sciences Faculty Research and Publications

The hypothalamic paraventricular nucleus (PVN) regulates numerous homeostatic systems and functions largely under the influence of forebrain inputs. Glutamate is a major neurotransmitter in forebrain, and glutamate neurosignaling in the PVN is known to mediate many of its functions. Previous work showed that vesicular glutamate transporters (VGluTs; specific markers for glutamatergic neurons) are expressed in forebrain sites that project to the PVN; however, the extent of this presumed glutamatergic innervation to the PVN is not clear. In the present study retrograde FluoroGold (FG) labeling of PVN-projecting neurons was combined with in situ hybridization for VGluT1 and VGluT2 mRNAs to identify …

Effect Of Animal Facility Construction On Basal Hypothalamic-Pituitary-Adrenal And Renin-Aldosterone Activity In The Rat, Hershel Raff, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Eric P. Cohen

Biomedical Sciences Faculty Research and Publications

Nearby construction can cause subtle, but important activation of the hypothalamic-pituitary-adrenal axis in laboratory rats.

Although loud noise and intense vibration are known to alter the behavior and phenotype of laboratory animals, little is known about the effects of nearby construction. We studied the effect of a nearby construction project on the classic stress hormones ACTH, corticosterone, renin, and aldosterone in rats residing in a barrier animal facility before, for the first 3 months of a construction project, and at 1 month after all construction was completed. During some of the construction, noise and vibrations were not obvious to investigators …

Repeated N-Acetyl Cysteine Reduces Cocaine Seeking In Rodents And Craving In Cocaine-Dependent Humans, Shelley L. Amen, Linda B. Piacentine, Muhammad E. Ahmad, Shi-Jiang Li, John R. Mantsch, Robert C. Risinger, David A. Baker

Biomedical Sciences Faculty Research and Publications

Addiction is a chronic relapsing disorder hypothesized to be produced by drug-induced plasticity that renders individuals vulnerable to craving-inducing stimuli such as re-exposure to the drug of abuse. Drug-induced plasticity that may result in the addiction phenotype includes increased excitatory signaling within corticostriatal pathways that correlates with craving in humans and is necessary for reinstatement in rodents. Reduced cystine–glutamate exchange by system x_c– appears to contribute to heightened excitatory signaling within the striatum, thereby posing this as a novel target in the treatment of addiction. In the present report, we examined the impact of repeated N-acetyl cysteine, …

The Effect Of High Dose Total Body Irradiation On Acth, Corticosterone, And Catecholamines In The Rat, Eric P. Cohen, Eric D. Bruder, William E. Cullinan, Dana R. Ziegler, Hershel Raff

Biomedical Sciences Faculty Research and Publications

Total body irradiation (TBI) or partial body irradiation is a distinct risk of accidental, wartime, or terrorist events. Total body irradiation is also used as conditioning therapy before hematopoietic stem cell transplantation. This therapy can result in injury to multiple tissues and might result in death as a result of multiorgan failure. The hypothalamic–pituitary–adrenal (HPA) axis could play a causative role in those injuries, in addition to being activated under conditions of stress. In a rat model of TBI, we have established that radiation nephropathy is a significant lethal complication, which is caused by hypertension and uremia. The current study …