Medicine and Health Sciences Commons^™

Suppression Of Rhog Activity Is Mediated By A Syndecan 4–Synectin–Rhogdi1 Complex And Is Reversed By Pkcα In A Rac1 Activation Pathway, Arye Elfenbein, John M. Rhodes, Julia Meller, Martin A. Schwartz, Michiyuki Matsuda, Michael Simons

Dartmouth Scholarship

Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive …

Olanzapine And Risperidone Disrupt Conditioned Avoidance Responding In Phencyclidine-Pretreated Or Amphetamine-Pretreated Rats By Selectively Weakening Motivational Salience Of Conditioned Stimulus, Ming Li, Wei He, Alexa Mead

Department of Psychology: Faculty Publications

The rat conditioned avoidance response model is a well-established preclinical behavioral model predictive of antipsychotic efficacy. All clinically approved antipsychotic drugs disrupt conditioned avoidance responding – a feature that distinguishes them from other psychotherapeutics. We previously showed that the typical antipsychotic drug haloperidol disrupts avoidance responding by progressively attenuating the motivational salience of the conditioned stimulus (CS) in normal rats. In this study, using two pharmacological rat models of schizophrenia [e.g. phencyclidine (PCP) or amphetamine sensitization], we examined whether atypicals such as olanzapine or risperidone disrupt avoidance responding through the same behavioral mechanism. Rats were first pretreated with PCP, amphetamine, …

Ranolazine Attenuates Behavioral Signs Of Neuropathic Pain, Harry J. Gould Iii, Colleen J. Garrett, Renee R. Donahue, Dennis Paul, Ivan Diamond, Bradley K. Taylor

Renee R. Donahue

Ranolazine modulates the cardiac voltage-gated sodium channel (NaV 1.5) and is approved by the FDA in the treatment of ischemic heart disease. Ranolazine also targets neuronal (NaV 1.7, 1.8) isoforms that are implicated in neuropathic pain. Therefore, we determined the analgesic efficacy of ranolazine in a preclinical animal model of neuropathic pain. Both intraperitoneal and oral administration of ranolazine dose-dependently inhibited the mechanical and cold allodynia associated with spared nerve injury, without producing ataxia or other behavioral side effects. These data warrant clinical investigation of the potential use of ranolazine in the treatment of neuropathic pain.

An Investigation Of The Behavioral Mechanisms Of Antipsychotic Action Using A Drug-Drug Conditioning Paradigm, Ming Li, Wei He, Alexa Mead

Department of Psychology: Faculty Publications

Antipsychotic drugs at noncataleptic doses selectively suppress conditioned avoidance response in rats. In our previous study, we had used a two-way active avoidance response paradigm to show that the antipsychotic-induced interoceptive state is one of the mechanisms underlying the avoidance-disruptive effect of antipsychotics. In this study, we sought to further examine this mechanism using a novel drug-drug conditioning procedure. We made use of the fact that both the typical neuroleptic haloperidol and the atypical neuroleptic olanzapine disrupt conditioned avoidance responding, whereas chlordiazepoxide (an anxiolytic) does not. We reasoned that if the antipsychotic interoceptive state is important in causing a disruption …

The Effect Of Neuronal Nitric Oxide Synthase Inhibitor 7-Nitroindazole On The Cell Death Induced By Zinc Administration In The Brain Of Rats, M. Fati̇h Gökçe, Faruk Bağirici, Şeri̇f Demi̇r, M. Ömer Bostanci, Aysel Güven

Turkish Journal of Medical Sciences

Aim: To evaluate the effect of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) on hippocampal cell loss induced by zinc hemisulfate salt (ZnSO4·7H2O) treatment. Materials and Methods: Rats were divided into 3 groups (n = 21; 7 rats in each group): Control, Zinc, and Zinc+7-NI. In the Zinc and Zinc+7-NI (pretreatment) groups, ZnSO4·7H2O was applied intracortically to the left sensory motor cortex. The 7-NI (50 mg/kg) was injected into the third group (Zinc+7-NI) intraperitoneally 20 min prior to zinc application and daily for the next 7 days. Cell loss in the left and right hippocampal hemispheres was quantified …

The Effect Of Vasoconstrictors On Oxygen Consumption In Resting And Contracting Skeletal Muscle Of The Autologous Pump-Perfused Rat Hindlimb, Andrew Hoy, Peter L. Mclennan, Gregory E. Peoples

Graduate School of Medicine - Papers (Archive)

No abstract provided.

Glutathione And Catalase Suppress Tgfß-Induced Cataract-Related Changes In Cultured Rat Lenses And Lens Epithelial Explants, Coral G. Chamberlain, Kylie J. Mansfield, Anna Cerra

Graduate School of Medicine - Papers (Archive)

Purpose: The damaging effects of oxidative stress and transforming growth factor-β (TGFβ)-induced transdifferentiation of lens epithelial cells have both been implicated independently in the etiology of cataract. The aim of this study was to investigate whether the presence of antioxidant systems in the lens influences the ability of lens epithelial cells to respond to TGFβ.

Methods: Whole lenses from young rats were cultured with or without TGFβ in the presence or absence of reduced glutathione (GSH). Lens epithelial explants from weanling rats were used to investigate the effects of GSH and catalase on TGFβ-induced cataract-related changes. Lenses were monitored for …

Etofenamate And Anastomoses Of The Colon In Rats, Aydin İnan, Önder Sürgi̇t, Meral Şen, Ayhan Akpinar, Mi̇kdat Bozer

Turkish Journal of Medical Sciences

Aim: Non-steroidal anti-inflammatory drugs have been used for many years due to their analgesic and anti-inflammatory properties. They have also been used for postoperative analgesia. We aimed to study the effects of etofenamate, a non-steroidal anti-inflammatory drug, on the healing of colonic anastomoses in rats. Materials and methods: Sprague-Dawley rats were used in this study. Resection and anastomosis were performed on the distal colon. The etofenamate group received 30 mg/kg etofenamate and the control group received 0.1 mL of 0.9% NaCl intramuscularly daily. Bursting pressures of anastomoses and hydroxyproline levels of perianastomotic tissues were determined on days 3 and 7. …

Myocardial Hsp70 Phosphorylation And Pkc-Mediated Cardioprotection Following Exercise, C.W. Melling, David Thorp, Kevin Milne, Earl Noble

Jamie Melling

Both protein kinase C (PKC) activation and Hsp70 expression have been shown to be key components for exercise-mediated myocardial protection during ischemia–reperfusion injury. Given that Hsp70 has been shown to undergo inducible phosphorylation in striated muscle and liver, we hypothesized that PKC may regulate myocardial Hsp70 function and subsequent exercise-conferred cardioprotection through this phosphorylation. Hence, acute exercise of male Sprague–Dawley rats (30 m/min for 60 min at 2% grade) was employed to assess the role of PKC and its selected isoforms in phosphorylation of Hsp70 and protection of the myocardium during ischemia-reperfusion injury. It was observed that administration of the …

Pathological Alterations In Gabaergic Interneurons And Reduced Tonic Inhibition In The Basolateral Amygdala During Epileptogenesis, Michael A. Rogawski, Brita Fritsch, Felicia Qashu, T. H. Figueiredo, Vicki Aroniadou-Anderjaska, Maria F.M. Braga

Michael A. Rogawski

An acute brain insult such as traumatic head/brain injury, stroke, or an episode of status epilepticus can trigger epileptogenesis, which, after a latent, seizure-free period, leads to epilepsy. The discovery of effective pharmacological interventions that can prevent the development of epilepsy requires knowledge of the alterations that occur during epileptogenesis in brain regions that play a central role in the induction and expression of epilepsy. In the present study, we investigated pathological alterations in GABAergic interneurons in the rat basolateral amygdala (BLA), and the functional impact of these alterations on inhibitory synaptic transmission, on days 7 to 10 after status …