Medical Sciences Commons^™

Inhibition Of Food Intake By Pacap In The Hypothalamic Ventromedial Nuclei Is Mediated By Nmda Receptors, Jon M. Resch, Brian Maunze, Kailynn A. Phillips, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Central injections of pituitary adenylate cyclase-activating polypeptide (PACAP) into the ventromedial nuclei (VMN) of the hypothalamus produce hypophagia that is dependent upon the PAC1 receptor; however, the signaling downstream of this receptor in the VMN is unknown. Though PACAP signaling has many targets, this neuropeptide has been shown to influence glutamate signaling in several brain regions through mechanisms involving NMDA receptor potentiation via activation of the Src family of protein tyrosine kinases. With this in mind, we examined the Src-NMDA receptor signaling pathway as a target for PACAP signaling in the VMN that may mediate its effects on feeding behavior. …

Nature Of The Neurotoxic Membrane Actions Of Amyloid-Β On Hippocampal Neurons In Alzheimer's Disease, Fernando J. Sepúlveda, Humberto Fierro, Eduardo Fernandez, Carolina Castillo, Robert W. Peoples, Carlos Opazo, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

The mechanism by which amyloid-β (Aβ) produces brain dysfunction in patients with Alzheimer's disease is largely unknown. According to previous studies, Aβ might share perforating properties with gramicidin, a well-accepted membrane-disrupting peptide. Therefore, we hypothesize that the key steps leading to synaptotoxicity by Aβ and gramicidin involve peptide aggregation, pore formation, and calcium dysregulation. Here, we show that Aβ and gramicidin form aggregates enriched in β-sheet structures using electron microscopy, and Thioflavin and Congo Red staining techniques. Also, we found that Aβ and gramicidin display fairly similar actions in hippocampal cell membranes, i.e. inducing Ca²⁺ entry and synaptoxicity characterized …

Fgf-2 Induces Neuronal Death Through Upregulation Of System Xc-, Xiaoqian Liu, Rebecca Albano, Doug Lobner

Biomedical Sciences Faculty Research and Publications

The cystine/glutamate antiporter (system xc-) transports cystine into cell in exchange for glutamate. Fibroblast growth factor-2 (FGF-2) upregulates system xc- selectively on astrocytes, which leads to increased cystine uptake, the substrate for glutathione production, and increased glutamate release. While increased intracellular glutathione can limit oxidative stress, the increased glutamate release can potentially lead to excitotoxicity to neurons. To test this hypothesis, mixed neuronal and glial cortical cultures were treated with FGF-2. Treatment with FGF-2 for 48 h caused a significant neuronal death in these cultures. Cell death was not observed in neuronal-enriched cultures, or astrocyte-enriched …

Neurobiological Mechanisms That Contribute To Stress-Related Cocaine Use, John R. Mantsch, Oliver Vranjkovic, Robert C. Twining, Paul J. Gasser, Jayme R. Mcreynolds, Jordan M. Blacktop

Biomedical Sciences Faculty Research and Publications

The ability of stressful life events to trigger drug use is particularly problematic for the management of cocaine addiction due to the unpredictable and often uncontrollable nature of stress. For this reason, understanding the neurobiological processes that contribute to stress-related drug use is important for the development of new and more effective treatment strategies aimed at minimizing the role of stress in the addiction cycle. In this review we discuss the neurocircuitry that has been implicated in stress-induced drug use with an emphasis on corticotropin releasing factor actions in the ventral tegmental area (VTA) and an important pathway from the …

Intrahypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide Regulates Energy Balance Via Site-Specific Actions On Feeding And Metabolism, Jon Resch, Brian Maunze, Adriana K. Gerhardt, Samuel K. Magnuson, Kailynn A. Phillips, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Numerous studies have demonstrated that both the hypothalamic paraventricular nuclei (PVN) and ventromedial nuclei (VMN) regulate energy homeostasis through behavioral and metabolic mechanisms. Receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) are abundantly expressed in these nuclei suggesting PACAP may be critical for the regulation of feeding behavior and body weight. To characterize the unique behavioral and physiological responses attributed to select hypothalamic cell groups, PACAP was site-specifically injected into the PVN or VMN. Overall food intake was significantly reduced by PACAP at both sites, however meal pattern analysis revealed only injections into the PVN produced significant reductions in meal size, …

Oral Branched-Chain Amino Acid Supplements That Reduce Brain Serotonin During Exercise In Rats Also Lower Brain Catecholamines, Sujean Choi, Briana Disilvio, Madelyn H. Fernstrom, John D. Fernstrom

Biomedical Sciences Faculty Research and Publications

Exercise raises brain serotonin release and is postulated to cause fatigue in athletes; ingestion of branched-chain amino acids (BCAA), by competitively inhibiting tryptophan transport into brain, lowers brain tryptophan uptake and serotonin synthesis and release in rats, and reputedly in humans prevents exercise-induced increases in serotonin and fatigue. This latter effect in humans is disputed. But BCAA also competitively inhibit tyrosine uptake into brain, and thus catecholamine synthesis and release. Since increasing brain catecholamines enhances physical performance, BCAA ingestion could lower catecholamines, reduce performance and thus negate any serotonin-linked benefit. We therefore examined in rats whether BCAA would reduce both …

Suprachiasmatic Astrocytes Modulate The Circadian Clock In Response To Tnf-Α, José M. Duhart, María Juliana Leone, Natalia Paladino, Jennifer A. Evans, Oscar Castanon-Cervantes, Alec J. Davidson, Diego A. Golombek

Biomedical Sciences Faculty Research and Publications

The immune and the circadian systems interact in a bidirectional fashion. The master circadian oscillator, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, responds to peripheral and local immune stimuli, such as proinflammatory cytokines and bacterial endotoxin. Astrocytes exert several immune functions in the CNS, and there is growing evidence that points toward a role of these cells in the regulation of circadian rhythms. The aim of this work was to assess the response of SCN astrocytes to immune stimuli, particularly to the proinflammatory cytokine TNF-α. TNF-α applied to cultures of SCN astrocytes from Per2^luc knockin mice altered …

Primary Blast Traumatic Brain Injury In The Rat: Relating Diffusion Tensor Imaging And Behavior, Matthew D. Budde, Alok Shah, Michael Mccrea, William E. Cullinan, Frank A. Pintar, Brian D. Stemper

Biomedical Sciences Faculty Research and Publications

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and …

The Hiv-1 Protein Vpr Targets The Endoribonuclease Dicer For Proteasomal Degradation To Boost Macrophage Infection, Laurieann Klockow, Hamayun J. Sharifi, Xiaoyun Wen, Meg Flagg, Andrea K.M. Furuya, Michael Nekorchuk, Carlos M.C. De Noronha

Biomedical Sciences Faculty Research and Publications

The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4^DCAF1 ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4^DCAF1. Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4^DCAF1. We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T …

Environmental Circadian Disruption Elevates The Il-6 Response To Lipopolysaccharide In Blood, Kandis L. Adams, Oscar Castanon-Cervantes, Jennifer A. Evans, Alec J. Davidson

Biomedical Sciences Faculty Research and Publications

The immune system is regulated by circadian clocks within the brain and immune cells. Environmental circadian disruption (ECD), consisting of a 6-h phase advance of the light:dark cycle once a week for 4 weeks, elevates the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. This indicates that circadian disruption adversely affects immune function; however, it remains unclear how the circadian system regulates this response under ECD conditions. Here, we develop an assay using ex vivo whole-blood LPS challenge to investigate the circadian regulation of immune responses in mice and to determine the effects of ECD on these …

Corticosterone Acts In The Nucleus Accumbens To Enhance Dopamine Signaling And Potentiate Reinstatement Of Cocaine Seeking, Evan N. Graf, Robert A. Wheeler, David A. Baker, Amanda L. Ebben, Jonathan E. Hill, Jayme R. Mcreynolds, Mykel A. Robble, Daniel S. Wheeler, John Mantsch, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was …

Prefrontal Activity Links Nonoverlapping Events In Memory, Marieke R. Gilmartin, Hiroyuki Miyawaki, Fred J. Helmstetter, Kamran Diba

Biomedical Sciences Faculty Research and Publications

The medial prefrontal cortex (mPFC) plays an important role in memory. By maintaining a working memory buffer, neurons in prelimbic (PL) mPFC may selectively contribute to learning associations between stimuli that are separated in time, as in trace fear conditioning (TFC). Until now, evidence for this bridging role was largely descriptive. Here we used optogenetics to silence neurons in the PL mPFC of rats during learning in TFC. Memory formation was prevented when mPFC was silenced specifically during the interval separating the cue and shock. Our results provide support for a working memory function for these cells and indicate that …

Nr2a- And Nr2b-Containing Nmda Receptors In The Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, And Contextual Fear Conditioning, Marieke R. Gilmartin, Janine L. Kwapis, Fred J. Helmstetter

Biomedical Sciences Faculty Research and Publications

Activation of N-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially regulate these two fear memories. Here we show that NR2A-containing NMDARs mediate trace, delay, and contextual fear memories, but NR2B-containing NMDARs are required only for trace conditioning, consistent with a role for PL mPFC in working memory.

Evidence For Covalent Linkage Between Some Plasma Α2-Antiplasmin Molecules And Aα Chains Of Circulating Fibrinogen, Michael W. Mosesson, Trudy Holyst, Irene Hernandez, Kevin R. Siebenlist

Biomedical Sciences Faculty Research and Publications

Plasma alpha₂-antiplasmin (α₂AP) is a single-chain serine protease inhibitor acting mainly through the fibrinolytic system. Its physiological importance is underscored by the observation that homozygous α₂AP deficiency results in a severe hemorrhagic disorder due to rapid fibrin clot lysis (hyperfibrinolysis).

Reduction In Phencyclidine Induced Sensorimotor Gating Deficits In The Rat Following Increased System Xc − Activity In The Medial Prefrontal Cortex, Victoria Lutgen, Krista Qualmann, Jon M. Resch, Linghai Kong, Sujean Choi, David A. Baker

Biomedical Sciences Faculty Research and Publications

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System x_c ⁻, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis.

Objectives: Our goal was to determine whether increased system x_c ⁻ activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating.

Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system x_c ⁻, in the prefrontal cortex. Prepulse inhibition was …

A Novel Alcohol-Sensitive Position In The M3 Domain Of The Nmda Receptor Glun2b Subunit, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

No abstract provided.

Sites Of Alcohol Action At The Glun1/Glun2b Nmda Receptor M3-M4 Domain Intersubunit Interfaces, Yuanhao Zhao, M. Wu, Hong Ren, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-D-aspartate (NMDA) receptor has been shown to be one of the most important target sites of alcohol in the central nervous system. We and others have identified positions in the third and fourth membrane-associated (M) domains of both GluN1 and GluN2A subunits that influence alcohol sensitivity. In the structural model of the NMDA receptor based upon the related GluA2 receptor, the outward face of the M3 domain of one subunit type is oriented toward the M4 domain of the other subunit type. We recently reported that four pairs of alcohol-sensitive amino acid positions in GluN1/GluN2A NMDA receptors interact at …

Interactions Among Positions In The Third And Fourth Membrane-Associated Domains At The Intersubunit Interface Of The N-Methyl-D-Aspartate Receptor Forming Sites Of Alcohol Action, Hong Ren, Yulin Zhao, Donard S. Dwyer, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-d-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The predicted structure of the NMDA receptor, based on that of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We tested the hypothesis that these positions interact to regulate receptor kinetics and ethanol sensitivity by using dual substitution mutants. In single-substitution mutants, we found that a position …

Glutathione-Mediated Neuroprotection Against Methylmercury Neurotoxicity In Cortical Culture Is Dependent On Mrp1, Travis Rush, Xiaoqian Liu, Andrew B. Nowakowski, David H. Petering, Doug Lobner

Biomedical Sciences Faculty Research and Publications

Methylmercury (MeHg) exposure at high concentrations poses significant neurotoxic threat to humans worldwide. The present study investigated the mechanisms of glutathione-mediated attenuation of MeHg neurotoxicity in primary cortical culture. MeHg (5 μM) caused depletion of mono- and disulfide glutathione in neuronal, glial and mixed cultures. Supplementation with exogenous glutathione, specifically glutathione monoethyl ester (GSHME) protected against the MeHg induced neuronal death. MeHg caused increased reactive oxygen species (ROS) formation measured by dichlorodihydrofluorescein (DCF) fluorescence with an early increase at 30 min and a late increase at 6 h. This oxidative stress was prevented by the presence of either GSHME or …

Cannabinoid Receptor Involvement In Stress-Induced Cocaine Reinstatement: Potential Interaction With Noradrenergic Pathways, Linda K. Vaughn, John R. Mantsch, Oliver Vranjkovic, G. Stroh, M. Lacourt, M. Kreutter, Cecilia J. Hillard

Biomedical Sciences Faculty Research and Publications

This study examined the role of endocannabinoid signaling in stress-induced reinstatement of cocaine seeking and explored the interaction between noradrenergic and endocannabinergic systems in the process. A well-validated preclinical model for human relapse, the rodent conditioned place preference assay, was used. Cocaine-induced place preference was established in C57BL/6 mice using injections of 15 mg/kg cocaine. Following extinction of preference for the cocaine-paired environment, reinstatement of place preference was determined following 6 min of swim stress or cocaine injection (15 mg/kg, i.p.). The role of endocannabinoid signaling was studied using the cannabinoid antagonist AM-251 (3 mg/kg, i.p.). Another cohort of mice …

Catecholamines In The Bed Nucleus Of The Stria Terminalis Reciprocally Respond To Reward And Aversion, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Background

Traditionally, norepinephrine has been associated with stress responses, whereas dopamine has been associated with reward. Both of these catecholamines are found within the bed nucleus of the stria terminalis (BNST), a brain relay nucleus in the extended amygdala between cortical/limbic centers, and the hypothalamic-pituitary-adrenal axis. Despite this colocalization, little is known about subsecond catecholamine signaling in subregions of the BNST in response to salient stimuli.

Methods

Changes in extracellular catecholamine concentration in subregions of the BNST in response to salient stimuli were measured within the rat BNST with fast-scan cyclic voltammetry at carbon-fiber microelectrodes.

Results

A discrete subregional distribution …

L-Tetrahydropalamatine: A Potential New Medication For The Treatment Of Cocaine Addiction, Jia Bei Wang​, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

Levo-tetrahydropalmatine (l-THP) is an active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis and has been approved and used in China for a number of clinical indications under the drug name Rotundine. The pharmacological profile of l-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, α adrenergic and serotonin receptors, suggests that it may have utility for treating cocaine addiction. In this review, we provide an overview of the pharmacological properties of l-THP and the evidence supporting its development as an anti-addiction medication. The results …

Stimulation Of The Hypothalamic Ventromedial Nuclei By Pituitary Adenylate Cyclase-Activating Polypeptide Induces Hypophagia And Thermogenesis, Jon M. Resch, Joanne P. Boisvert, Allison E. Hourigan, Christopher R. Mueller, Sun Shin Yi, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Numerous studies have demonstrated that the hypothalamic ventromedial nuclei (VMN) regulate energy homeostasis by integrating and utilizing behavioral and metabolic mechanisms. The VMN heavily express pituitary adenylate cyclase-activating polypeptide(PACAP) type I receptors (PAC1R). Despite the receptor distribution, most PACAP experiments investigating affects on feeding have focused on intracerebroventricular (icv) administration or global knockout mice. To identify the specific contribution of PACAP signaling in the VMN, we injected PACAP directly into the VMN and measured feeding behavior and indices of energy expenditure. Following an acute injection of PACAP, nocturnal food intake was significantly reduced for six hours after injections without evidence …

Glutamatergic Plasticity In Medial Prefrontal Cortex And Ventral Tegmental Area Following Extended-Access Cocaine Self-Administration, Behnam Ghasemzadeh, Preethi Vasudevan, Chad Giles, Anthony Purgianto, Chad Seubert, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

Glutamate signaling in prefrontal cortex and ventral tegmental area plays an important role in the molecular and behavioral plasticity associated with addiction to drugs of abuse. The current study investigated the expression and postsynaptic density redistribution of glutamate receptors and synaptic scaffolding proteins in dorsomedial and ventromedial prefrontal cortex and ventral tegmental area after cocaine self-administration. After 14 days of extended-access (6 h/day) cocaine self-administration, rats were exposed to one of three withdrawal regimen for 10 days. Animals either stayed in home cages (Home), returned to self-administration boxes with the levers withdrawn (Box), or underwent extinction training (Extinction). Extinction training …

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 …

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 …

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, …

Serotonin Mediated Changes In Corticotropin Releasing Factor Mrna Expression And Feeding Behavior Isolated To The Hypothalamic Paraventricular Nuclei, Joanne P. Boisvert, Tyler J. Boschuetz, Jon M. Resch, Christopher R. Mueller, Sujean Choi

Biomedical Sciences Faculty Research and Publications

Fenfluramine reduces hunger and promotes body weight loss by increasing central serotonin (5-HT) signaling. More recently, neuropeptides have been linked to the regulation of feeding behavior, metabolism and body weight. To examine possible interactions between 5-HT and neuropeptides in appetite control, fenfluramine (200 nmol/0.5 μl/side) was administered directly into the hypothalamic paraventricular nuclei (PVN) of male rats. Bilateral fenfluramine produced significant hypophagia and increased expression of PVN corticotropin releasing factor (CRF) mRNA and neuropeptide Y (NPY) mRNA in the arcuate nucleus within the first hour after drug administration. Fenfluramine's effects on feeding behavior and mRNA expression were blocked by PVN …