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Dive into the research topics where Thomas Stöhr is active.

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Featured researches published by Thomas Stöhr.


Psychopharmacology | 1995

Anxiety: a potential predictor of vulnerability to the initiation of ethanol self-administration in rats.

Rainer Spanagel; Alexandra Montkowski; K. Allingham; Thomas Stöhr; M. Shoaib; Florian Holsboer; Rainer Landgraf

Anxiolytic effects of ethanol have been proposed to be important factors in the initiation of ethanol consumption. To examine this hypothesis, drug-naive Wistar rats were tested in the elevated plusmaze to determine their initial level of anxiety. Based on their response, we separated the animals into anxious and non-anxious groups. After that, animals went through an oral ethanol self-administration procedure. Rats that were initially classified as anxious showed a significantly (P<0.01) higher intake and preference for ethanol during the initiation phase of the voluntary drinking procedure than non-anxious animals. In another experiment, intraperitoneal (IP) injections of ethanol (0.5–1.5 g/kg) produced dose-dependent anxiolytic effects in rats when tested in the elevated plus-maze procedure. Blood ethanol levels following IP injections during the plus-maze test were similar to those reached during the oral ethanol self-administration procedure, which shows that the rats indeed drank sufficient amounts of ethanol to experience its anxiolytic effects. These findings indicate that the basal level of anxiety plays an important role in vulnerability to alcohol drinking.


Cellular and Molecular Neurobiology | 1994

Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide treatment attenuates social defeat-induced anxiety in rats

Thomas Skutella; Alexandra Montkowski; Thomas Stöhr; Joseph Christopher Probst; Rainer Landgraf; Florian Holsboer; Gustav F. Jirikowski

Summary1. The neuropeptide corticotropin-releasing hormone (CRH) is the main mediator of the neuroendocrine and behavioral response to stress. End-capped phosphorothioate antisense and sense oligodeoxynucleotides (ODN) corresponding to the start coding region of rat CRH mRNA were infused intracerebroventricularly (30 µg/3 μl per injection) three times at 12 hr intervals. Six hours after the last injection rats were subjected to social defeat stress and subsequently tested on the elevated plus maze.2. Socially defeated CRH antisense-treated rats displayed markedly reduced anxiety-related behavior, as they spent significantly more time in the open arms of the plus maze compared to sense ODN- and vehicle-treated animals.3. In controls, social defeat evoked a stress-induced elevation of CRH mRNA and CRH in the hypothalamus and a significant increase in plasma corticotropin (ACTH) levels. These parameters were attenuated in antisense-injected rats.4. Our results suggest that CRH antisense treatment is effectively suppressing the neuroendocrine and behavioral effects of social defeat.


Arthritis Research & Therapy | 2007

Antinociceptive efficacy of lacosamide in the monosodium iodoacetate rat model for osteoarthritis pain

Bettina Beyreuther; Noëlle Callizot; Thomas Stöhr

The etiology of osteoarthritis is multifactorial, with inflammatory, metabolic, and mechanical causes. Pain in osteoarthritis is initiated by mild intra-articular inflammation and degeneration of articular cartilage and subchondral bone. The principle of treatment with acetaminophen or non-steroidal anti-inflammatory drugs is to reduce pain and improve joint function. Recently, animal models for osteoarthritic pain behavior have been established. The most frequently used rat model for analyzing properties of drugs on the pathology of osteoarthritis is the injection of the metabolic inhibitor monosodium iodoacetate into the joint, which inhibits the activity of glyceraldehyde-3-phosphate dehydrogenase in chondrocytes. Here, we characterize the effect on pain behavior of lacosamide, a member of a family of functionalized amino acids that are analogues of endogenous amino acids and D-serine, in the monosodium iodoacetate rat model for osteoarthritis in comparison to diclofenac and morphine. Lacosamide (3, 10, and 30 mg/kg) was able to reduce secondary mechanical allodynia and hyperalgesia similarly to morphine (3 mg/kg). In contrast, diclofenac (30 mg/kg) was only effective in reducing secondary mechanical hyperalgesia. During the first week, pain is induced mainly by inflammation in the iodoacetate model, but afterwards inflammation plays only a minor role in pain. Lacosamide was able to inhibit pain at days 3, 7 and 14 after induction of arthritis. This shows that lacosamide is able to reduce pain behavior induced by multiple mechanisms in animals.


Psychopharmacology | 1995

Strain differences in the rewarding and dopamine-releasing effects of morphine in rats

M. Shoaib; Rainer Spanagel; Thomas Stöhr; Toni S. Shippenberg

Studies examining differential sensitivity to psychoactive drugs in mice suggest that genotype may play a critical role. Furthermore, an involvement of genotype in mediating individual differences in sensitivity to the rewarding effects of several drugs of abuse has also been postulated. The aim of this study was to examine the conditioned rewarding and dopamine-releasing effects of morphine in two outbred rat strains commonly used in addiction research. Additionally, the behavioural and neuroendocrine responses of these strains to the stress of novelty were also examined. Basal locomotor activity was higher in Wistar rats than Sprague-Dawley following exposure to a novel environment. In contrast, elevations in plasma corticosteroid levels following novelty exposure did not differ between the two strains. In a counterbalanced place preference conditioning procedure, increasing doses of morphine (1.0–10.0 mg/kg SC) produced significant conditioned place preferences (CPP) in both Wistar and Sprague-Dawley strains. However, Wistar rats required a significantly larger dose of morphine (5.0 mg/kg) to produce a significant CPP than the Sprague-Dawley rats. In the latter strain, CPP occurred with doses of 3.0 mg/kg and greater. In parallel microdialysis experiments, both strains showed significant dose-related increases in dopamine release in the nucleus accumbens following acute morphine challenge (1.0–10.0 mg/kg SC). Again in Wistar rats, a larger dose of morphine was necessary to produce a significant increase in comparison to Sprague-Dawley rats. These results show that genetically distinct rat strains can show differential sensitivity to opioids, more specifically to drug-seeking responses.


European Journal of Pain | 2006

Lacosamide displays potent antinociceptive effects in animal models for inflammatory pain.

Thomas Stöhr; Eva Krause; Norma Selve

Lacosamide is a functionalized amino acid which was initially synthesized as an antiepileptic drug. In addition to its broad anti‐seizure activity, lacosamide was shown to display efficacy in animal models for neuropathic pain and is currently in phase III clinical development for the treatment of epilepsy and neuropathic pain. In order to further profile its antinociceptive properties, the effects of lacosamide on inflammatory pain in the formalin test, the carrageenan model and the adjuvant‐induced arthritis model were investigated.


Behavioural Brain Research | 1999

Stress- and corticosteroid-induced modulation of the locomotor response to morphine in rats.

Thomas Stöhr; Osborne F. X. Almeida; Rainer Landgraf; Toni S. Shippenberg; Florian Holsboer; Rainer Spanagel

Stress alters the sensitivity to drugs of abuse and is, therefore, considered to be an important contributory factor to drug-seeking behaviour. There is only a limited amount of information available on stress-induced alterations in the behavioural response to opioids. We thus evaluated the influences of different stressors (restraint, handling, social defeat) on the locomotor effects induced by morphine. Further the importance of additional factors such as the number of stress events or the delay between stress and locomotor testing on stress-induced alterations were evaluated. Since these modulatory effects of stress on the locomotor effects of morphine might be mediated via the release of endogenous corticosteroids we also tested the influence of repeated intermittent and chronic administration of corticosterone (CORT) and the synthetic corticosteroid dexamethasone (DEX) on the locomotor response to morphine. Enhanced morphine-induced locomotor activity was observed in response to the repeated application (three times) of all stressors: restraint, handling and social defeat. An augmentation of the locomotor effects of a low (1 and 5 mg/kg) but not of a high dose (10 mg/kg) of morphine was seen after three, but not after one stress event. In addition, the repeated application of restraint stress (three times) resulted in an augmentation of morphine-induced locomotor stimulation 3 days, but not 1 or 10 days , after the last stress event. Similarly the repeated intermittent and chronic administration of corticosteroids, in particular of DEX, increased morphines efficacy in stimulating locomotor activity. Our results show that stress is able to alter the locomotor stimulant effects of morphine in rats--a phenomenon called stress-induced behavioural sensitization. Moreover, these stress-induced alterations depend upon temporal factors such as number of stress events and the interval between stress and locomotor testing. Further, stress-induced CORT-release seems to be involved in stress-induced behavioural sensitization to morphine.


European Journal of Pharmacology | 1997

Centrally administered oligodeoxynucleotides in rats: occurrence of non-specific effects.

Bernd Schöbitz; Gita Pezeshki; Joseph Christopher Probst; Johannes M. H. M. Reul; Thomas Skutella; Thomas Stöhr; Florian Holsboer; Rainer Spanagel

We studied the effects of various intracerebroventricularly administered oligodeoxynucleotides on body temperature, locomotor activity, food intake and water consumption in rats during a 24 h period with a radio-telemetric system. Both complete phosphorothioate oligodeoxynucleotides and end-inverted oligodeoxynucleotides dose-dependently elevated body temperature, suppressed food and fluid intake and inhibited nighttime activity. Apparently these effects do not depend on the nucleotide sequence because antisense and sense arginine vasopressin and oxytocin oligodeoxynucleotides, as well as a missense oligodeoxynucleotide produced comparable changes in the autonomous and behavioral parameters. In control experiments neither contaminants from the chemical synthesis nor endotoxins produced such effects, whereas native DNA from salmon sperm did. Fever and sickness-like behavior in response to missense phosphorothioate oligodeoxynucleotides were accompanied by elevated concentrations of circulating corticosterone and by a marked increase in interleukin 6 mRNA in brain and spleen, indicating that centrally administered oligodeoxynucleotides stimulate the production of pyrogenic inflammatory mediators in both central nervous system and peripheral tissues. Our results indicate that centrally administered oligodeoxynucleotides produce beside their intended sequence-specific effects also transient and sequence-independent effects due to their nucleic acid structure.


Neuropharmacology | 2007

Antihyperalgesic efficacy of lacosamide in a rat model for muscle pain induced by TNF.

Bettina K. Beyreuther; Christian Geis; Thomas Stöhr; Claudia Sommer

Chronic muscle pain is a problem with high prevalence in clinical practice and its pharmacological treatment is difficult. There is a lack of animal models which reliably predict analgesic activity of drugs on muscle pain. Here we used intramuscular injection of tumor necrosis factor-alpha (TNF) in rats as a model of muscle pain. In this model we tested the antihyperalgesic action of lacosamide in comparison to the analgesics pregabalin and gabapentin. Mechanical withdrawal thresholds to muscle pressure were measured with an algesimeter exerting pressure on the gastrocnemius muscles previously injected with TNF. Fore limb grip strength was measured with a digital grip force meter after TNF injection into the biceps brachii muscles. A complete reversal of hyperalgesia was seen with lacosamide at 30mg/kg. Significant effects were also seen for pregabalin at 30 and 100mg/kg and gabapentin at 100mg/kg. In biceps muscle hyperalgesia, a significant reversal of hyperalgesia was seen with lacosamide at 10mg/kg. Significant effects were also seen for pregabalin and gabapentin at 100mg/kg. We could thus demonstrate in a rat model for myalgia that lacosamide effectively reduces muscular hyperalgesia and is somewhat more potent than gabapentin and pregabalin.


Journal of Neuroendocrinology | 1996

Morphine-induced locomotor and neurochemical stimulation is enhanced in transgenic mice with impaired glucocorticoid receptor function.

Rainer Spanagel; Thomas Stöhr; Nicholas Barden; Florian Holsboer

It has been suggested that the hypothalamic‐pituitary‐adrenocortical (HPA) system contributes to individual differences in sensitivity towards drug abuse. Therefore, we studied the effects of the prototypic drug morphine in transgenic mice with impaired glucocorticoid receptor function. This mouse model has a profoundly dysfunctional HPA feedback. Since morphine‐induced locomotor stimulation is positively correlated with the rewarding effects of morphine, we examined morphine‐induced locomotor activity of transgenic mice and control mice (B6C3F1), Because morphine‐induced locomotor activity depends on an intact mesolimbic system, dopaminergic (DAergic) neuronal activity was also estimated within the mesolimbic system. Results indicated that the activity after vehicle injection do not differ between these two mouse lines. Compared to vehicle injections, morphine (7.5 and 15mg/kg; i.p.) dose‐dependently increased motor activity for 3 h in control and transgenic mice. However, morphine‐induced locomotion was significantly more pronounced in transgenic mice. Further, morphine‐induced mesolimbic DAergic activity was enhanced in transgenic animals as compared to control animals. These results parallel endocrine data that show that the plasma ACTH level of transgenic mice reach higher levels compared to those levels observed in control mice after morphine injections. Altogether, this transgenic mouse line shows an enhanced locomotor‐stimulant effect to morphine, a response that is reflected by an enhanced DAergic activity within the mesolimbic system and is also associated with increased HPA activity. We submit that the dysregulation of the HPA system in these transgenic mice influences the enhanced vulnerability to drug‐seeking behavior.


Neuropharmacology | 2011

Lacosamide has protective disease modifying properties in experimental vincristine neuropathy.

Christian Geis; Bettina K. Beyreuther; Thomas Stöhr; Claudia Sommer

Pain and paresthesias are the most common symptoms of chemotherapy induced painful neuropathy (CIPN). Current treatment and preventive strategies of CIPN are ineffective, and the neuropathy may lead to discontinuation of anti-tumor therapy. Here we used experimental vincristine-induced neuropathy in rats to evaluate the disease modifying potential of lacosamide using a sustained release formulation and the acute treatment effects of a rapid release formulation. Pain behavior was assessed by withdrawal responses to von Frey hairs, acetone drops, the Randall-Selitto device, and to radiant heat. Neuropathy was assessed using electrophysiological recordings. Preventive lacosamide treatment (30 mg/kg subcutaneously b.i.d. for 17 days) was well tolerated, and pharmacokinetic analysis revealed a peak plasma concentration 2 h post-injection with a plasma half-life of approximately 3 h. Rats treated with lacosamide, in contrast to vehicle treated rats, did not develop vincristine-induced cold allodynia. Neurophysiology showed a delayed F-wave latency in vehicle treated rats, which was not present in lacosamide treated animals. We could thus demonstrate a protective disease modifying potency of lacosamide in an animal model of CIPN. Lacosamide may be a promising candidate for preventive treatment of CIPN in patients receiving chemotherapy with vinca alkaloids or platinum drugs.

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Toni S. Shippenberg

National Institute on Drug Abuse

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