Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rodent models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed1997

Metabolic effects of troglitazone in the Goto-Kakizaki rat, a non-obese and normolipidemic rodent model of non-insulin-dependent diabetes mellitus.

Troglitazone (TRG) is an orally active antidiabetic agent that increases insulin sensitivity in models of non-insulin-dependent diabetes mellitus (NIDDM), subsequently reducing hyperinsulinemia and hyperglycemia. We examined the effects of TRG on the development and severity of diabetes in the Goto-Kakizaki (GK) rat, a spontaneous, non-obese model of NIDDM. TRG was administered at a dose of 30 mg/kg/d beginning at 4 weeks of age. TRG-treated GK rats were evaluated against Wistar and untreated GK rats at 8, 12, and 16 weeks of age. Untreated GK rats were nonketotic, normolipidemic, hyperglycemic, and had normal fasting insulin levels compared with Wistar rats. TRG treatment decreased glycosylated hemoglobin levels in the GK rat independently of its effects on plasma insulin. In untreated GK rats, intravenous glucose tolerance tests (IVGTTs) showed a hyperglycemic response to glucose loading with severely impaired glucose disposal relative to Wistar controls. TRG treatment was successful in decreasing the glucose area under the curve (AUC) (P < .03) but did not improve glucose disposal, suggesting a direct hepatic effect. Ex vivo evaluation of hepatic glucose output (HGO) further supported a direct hepatic action, with 50% reduction in HGO in TRG-treated GK rats (P < .004). A euglycemic-hyperinsulinemic clamp performed at 16 weeks of age showed severe insulin resistance in the untreated GK rat, with a glucose infusion rate (GIR) 33% lower than in Wistar rats (P < .004). TRG treatment had no effect on this insulin resistance. These results indicate that TRG selectively decreases hepatic glucose production in this unique model of NIDDM independently of its action on peripheral insulin sensitivity or hyperlipidemia.

Animals↗
PubMed1999

GlycineB antagonists and partial agonists in rodent models of Parkinson's disease--comparison with uncompetitive N-methyl-D-aspartate receptor antagonist.

Antiparkinsonian-like activity of glutamate receptor antagonists (mostly of N-methyl-D-aspartate (NMDA) receptors) has been demonstrated in animals and for uncompetitive agents, also in humans. In the present study we investigated the potential antiparkinsonian-like activity of compounds acting at the glycine site of the NMDA receptor complex in three animal models of Parkinson's disease and compared them with the new uncompetitive NMDA receptor antagonist MRZ 2/579. Haloperidol-induced catalepsy was inhibited by the Merz glycine site antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 but not by another antagonist L-701,324 or the glycine site partial agonists ACPC and D-CS. None of the tested glycine site antagonists or partial agonists increased locomotor activity or potentiated L-DOPA responses in reserpine and alpha-MT treated rats. In rats with a unilateral 6-OHDA medial forebrain bundle lesion neither glycine site antagonists nor partial agonists affected rotations on their own or enhanced the contralateral rotations induced by L-DOPA. In contrast, the uncompetitive NMDA receptor antagonist MRZ 2/579 was active in all antiparkinsonian tests used in this study. Based on the present data the therapeutic potential of the glycine site antagonists and partial agonists tested for the treatment of Parkinson's disease is rather doubtful. Uncompetitive NMDA receptor antagonists seem to possess a better profile as antiparkinsonian agents.

Animals↗
PubMed1999

A rodent model of spontaneous stereotypy: initial characterization of developmental, environmental, and neurobiological factors.

Stereotypies are patterns of motor behavior that are repetitive, excessive, topographically invariant, and that lack any obvious function or purpose. In humans, stereotyped behaviors are associated with psychiatric, neurological, and developmental disorders. In animals, stereotypy has been frequently associated with adverse environmental circumstances and often related to alterations in striatal dopamine. To assess the development of stereotyped behaviors and to test the hypothesis that these behaviors are associated with environmental restriction, deer mice were housed in either standard laboratory cages or larger, enriched cages, and the development of stereotypy was followed from weaning over a 17-week period. Standard-caged deer mice engaged in stereotyped behaviors at a higher rate and developed these behaviors more quickly when compared to animals in enriched caging. Additionally, enriched caging was associated with higher rates of patterned running, whereas jumping and backward somersaulting were typically observed in standard cages. In addition, there was a significant effect of litter, but no effect of sex or cage, on the time to develop stereotypy. No differences were found in the density of either striatal D1 or D2 dopamine receptors or the concentration of striatal dopamine or its metabolites as a function of rearing condition or as a function of whether the animals developed stereotypy. These results characterize the development of stereotypies in this species, demonstrate the importance of environmental conditions in the genesis of stereotypy, and suggest that alterations in striatal dopamine content or dopamine receptor density do not account for the expression of stereotyped behaviors in this model.

Aging↗
PubMed2000

Inheritance of ventilatory behavior in rodent models.

Studies in mice and rats support the hypothesis that ventilation and its components (frequency and tidal volume) are determined to a significant extent by genetic mechanisms. The question can no longer be 'is there a genetic effect?' but rather 'how strong is the genetic component?' and 'what genes are involved?' The computational analyses of selectively bred animals now offer powerful tools to begin to dissect the genetic factors that track with ventilatory traits. Control of the conditions in the colony and in the laboratory are keys to reducing the environmental 'noise' and increasing the likelihood of detecting gene loci that correlate quantitatively with phenotype values before and during the response to chemosensory challenges. Knowing the chromosomal location of genes for ventilation will then permit the identification of proteins systems responsible for the structural and functional components for respiration.

Animals↗
PubMed2001

Rodent models of susceptibility: what is their place in inhalation toxicology?

There is renewed interest in inhalation toxicology regarding 'susceptibility' as associated with host variables, including genetics, age, diet, and disease. This interest derives from epidemiology that shows air pollution-related human mortality/morbidity, especially among individuals with cardiopulmonary disease. Several animal models with experimental or genetically-based cardiopulmonary diseases are now being incorporated into inhalation toxicology studies to investigate mechanisms that underlie host susceptibility. However, current models have strengths and limitations as to how they mimic the essential features of human diseases. To date, animal models of pulmonary hypertension, bronchitis, asthma, and cardiovascular disease, but not emphysema, appear to exhibit greater susceptibility to air pollution particulate matter. As in humans, host susceptibility appears to involve multiple genetic and environmental factors, and is poorly understood, but the database of information is growing rapidly. As existing models gain wider use, our understanding of the models will improve and encourage refinements/development of models that integrate both genetic and environmental factors to better mimic the human condition.

Administration, Inhalation↗
PubMed2003

Behavioral measures of alcohol self-administration and intake control: rodent models.

This review provides a brief historical overview of the behavioral paradigms that have been used to study alcohol consumption using rats as subjects, and then critically evaluates these models' ability to address the complexities involved in ethanol-seeking and self-administration. Many of these models have been influenced by a "behavioral pharmacology" approach, and therefore have studied oral ethanol reinforcement in a manner similar to food and water reinforcement. Because of this, these models have failed to adequately assess the complex seeking responses that are an integral part of ethanol-motivated behaviors. As an alternative, an appetitive-consummatory approach that procedurally separates and measures the two phases of behavior is suggested, and recent data using this model are reviewed. It is important that animal models that are to be used to evaluate underlying physiological mechanisms of the control of ethanol self-administration accurately address all of the complex behaviors that are involved in intake control.

Alcohol Drinking↗
PubMed2004

Neurotrophic factors and CNS disorders: findings in rodent models of depression and schizophrenia.

Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are proteins involved in neuronal survival and plasticity of dopaminergic, cholinergic and serotonergic neurons in the central nervous system (CNS). Loss of neurons in specific brain regions has been found in depression and schizophrenia, and this chapter summarizes the findings of altered neurotrophins in animal models of those two disorders under baseline condition and following antidepressive and antipsychotic treatments. In a model of depression (Flinders sensitive line/Flinders resistant line; FSL/FRL rats), increased NGF and BDNF concentrations were found in frontal cortex of female, and in occipital cortex of male 'depressed' FSL compared to FRL control rats. Using the same model, the effects of electroconvulsive stimuli (ECS) and chronic lithium treatment on brain NGF, BDNF and glial cell line-derived neurotrophic factors were investigated. ECS and lithium altered the brain concentrations of neurotrophic factors in the hippocampus, frontal cortex, occipital cortex and striatum. ECS mimic the effects of electroconvulsive therapy (ECT) that is an effective treatment for depression and also schizophrenia. Since NGF and BDNF may also be changed in the CNS of animal models of schizophrenia, we investigated whether treatment with antipsychotic drugs (haloperidol, risperidone, and olanzapine) affects the constitutive levels of NGF and BDNF in the CNS. Both typical and atypical antipsychotic drugs altered the regional brain levels of NGF and BDNF. Other studies also demonstrated that these drugs differentially altered neurotrophin mRNAs. Overall, these studies indicate that alteration of brain level of NGF and BDNF could constitute part of the biochemical alterations induced by antipsychotic drugs.

Animals↗
PubMed1995

Role of endothelium-derived relaxing factor in the maintenance of renal blood flow in a rodent model of chronic hydronephrosis.

OBJECTIVES: To define the role of endothelium-derived relaxing factor (EDRF) in the regulation of renal hemodynamics in the hydronephrotic kidney. METHODS: Experiments were performed in control rats and in rats that had undergone unilateral ureteral ligation 6 weeks before. Renal blood flow was monitored before and after inhibition of EDRF synthesis in the control and hydronephrotic animals. Videomicroscopy was also performed in hydronephrotic animals to observe directly the effect of inhibition of EDRF synthesis on the renal microcirculation. RESULTS: Inhibition of EDRF synthesis resulted in a 61% decrease in renal blood flow in the control animals compared with only a 27% decrease for the hydronephrotic animals. The videomicroscopy studies demonstrated that inhibition of EDRF synthesis results in significant vasoconstriction of the preglomerular and postglomerular resistance vessels. CONCLUSIONS: Although EDRF continues to play a significant role in the maintenance of renal blood flow in the chronically obstructed kidney, EDRF synthesis by the renal vascular endothelium may be reduced in this setting, contributing to ischemic renal atrophy.

Acetylcholine↗
PubMed2000

A rodent model of cocaine abstinence syndrome.

This study introduces a rat model of cocaine abstinence syndrome based on quantitation of spontaneously emitted behaviors following termination of continuous drug exposure (analogous to established methods of assessing morphine and nicotine abstinence). Groups of eight male S-D rats were infused SC for 7 days via an osmotic minipump with saline alone or with 40 or 60 mg/kg/day cocaine HCl. Pumps were removed and rats were observed at 12, 24, 36, and 48 h postremoval. Each 15-min observation employed a checklist of abstinence signs including ptosis, chews, teeth chatters, gasps, writhes, seminal ejaculations, head shakes, and tremors. The high infusion rate group displayed significantly more signs than the low infusion rate group, which in turn, displayed significantly more signs than the saline group. Cocaine injection significantly reduced signs by 83.3%, while saline injection reduced them by only 4.9%. In another experiment, rats infused with 60 mg/kg/day showed significantly more signs 36 h postinfusion than before infusion, during infusion and 84 h postinfusion. Finally, 6.5 days of infusion resulted in significantly more abstinence signs than did 1.5 days of infusion. This rapid and simple model quantitated cocaine abstinence syndrome in a manner that was cocaine-reversible and related to the rate and duration of drug infusion.

Animals↗
PubMed1998

Individual differences in sucrose intake predict behavioral reactivity in rodent models of anxiety.

We have previously shown that individual differences in oral sucrose consumption are predictive of behavioral reactivity of rats in the elevated plus-maze (EPM). The present experiments were designed to replicate the EPM results and to extend them to another animal model of anxiety, the acoustic startle reflex (ASR) paradigm. In two experiments, sucrose consumption was assessed in separate groups of rats across eight daily 1-h feeding sessions. Animals were designated as either low (LSF) or high sucrose feeders (HSF) based on a median split of their sucrose intake on the final test day. Following this assay, animals were tested in the EPM in Experiment 1, and in the ASR paradigm in Experiment 2. Results from Experiment 1 replicated our previous findings and showed that the percentage of time spent on, and entries into, open arms was significantly lower in LSF than HSF. Further, results from Experiment 2 revealed a significantly augmented startle response to acoustic stimuli (94-108 dB SPL) in LSF compared to HSF. These data provide converging evidence to support the notion that individual differences in baseline levels of oral sucrose consumption are predictive of anxious behaviors in rats.

Acoustic Stimulation↗
PubMed1997

Use of differential normal pulse voltammetry for the measurement of locus coeruleus catecholaminergic metabolism in an acute anaesthetized rodent model of allodynia: effect of mexiletine.

Neuropathic pain can be triggered by non-painful stimuli (e.g., light touch), a sensory abnormality termed allodynia. The acute blockade of spinal glycine receptors with intrathecal strychnine induces a reversible allodynia-like state in the rat. We describe the application of in vivo differential normal pulse voltammetry with carbon fibre micro-electrodes for monitoring the catechol oxidation current (CAOC) of the locus coeruleus (LC) in the strychnine model of allodynia. In addition, we tested the effect of mexiletine, a drug useful in the management of clinical neuropathic pain in this model. Our results show that somatosensory processing in the spinal cord of urethane-anaesthetized rats is radically altered during glycine receptor blockade such that the normally innocuous stimulus of hair deflection causes the marked activation of the LC as determined using in vivo differential normal pulse voltammetry. Mexiletine suppressed the LC and cardiovascular responses of strychnine induced allodynia. Results of this study indicate that LC CAOC, an index of LC neuronal activity: (a) is a sensitive biochemical index of strychnine-allodynia; (b) is temporally correlated with the cardiovascular and motor responses evoked by hair deflection during glycine receptor blockade; and (c) can be used to quantitate allodynia in the strychnine model.

Anesthesia↗
PubMed2002

Rodent models of prefrontal cortical function.

In this article, we consider whether studies in rats can provide useful information regarding the debate about the functions of the primate prefrontal cortex. At a superficial level, comparison of regional specializations within the prefrontal cortices of different species suggests functional correspondence. Unfortunately, the nature of functional specialization in primate prefrontal cortex is controversial, and data supporting the idea of homology between specific areas of rat and primate prefrontal cortex are weak. Nevertheless, we argue here that studies of the computational functions within the relatively undifferentiated prefrontal cortex of rats can shed light on processing in primate prefrontal cortex.

Animals↗
PubMed2000

Memory of an operant response and of depressed mood retained in activation states of 5-HT(1A) receptors: evidence from rodent models.

Three series of studies were conducted to specify the role of 5-HT(1A) receptors in memory; using selective ligands that differentially activate 5-HT(1A) receptors, it was determined whether a change in the activation state of these receptors can lead to deficient retrieval, and whether a so-produced deficit can occur in an animal model of depression. First, in vitro studies of [35S]GTPgammaS binding responses identified ligands that differentially activate 5-HT(1A) receptors in rat hippocampus. WAY 100635, 8-OH-DPAT and flesinoxan induced 5-HT(1A) receptor activation that amounted to -2, +50 and +63%, respectively, of that produced by 5-HT. Second, we determined whether changes in the activation state of 5-HT(1A) receptors could impair the retrieval of an operant response in vivo. Rats treated with either a 5-HT(1A) receptor ligand or saline were trained to lever press for milk reward, and were then tested for retrieval with either the same or another treatment. Animals trained with 8-OH-DPAT retrieved the response when tested in the same state, but not when tested in the saline state, and vice versa. Rats trained with 0.16 mg/kg of 8-OH-DPAT also retrieved the response when tested with the other intermediate-efficacy ligand flesinoxan (0.63 mg/kg), but not when tested in a state of lower-magnitude activation (i.e. with 0.16 mg/kg of WAY 100635). Animals trained with 0.16 mg/kg of WAY 100635 retrieved the response when tested in this same state or with saline, but not when tested in a state of intermediate-magnitude activation (i.e. with 0.16 mg/kg of 8-OH-DPAT). Finally, studies using the forced swimming paradigm indicated that the retrieval of learned immobility was similarly dependent upon the activation state of 5-HT(1A) receptors. The findings indicate that changes in activation states of 5-HT(1A) receptors can impair the retrieval of learned responses. It is suggested that depression may in part be acquired in the course of ontogeny and may be available for retrieval in the same but not in other states; various biological rhythms conceivably define such states.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Efficacy of rabies immunoglobulins in an experimental post-exposure prophylaxis rodent model.

In a recently published Syrian hamster animal challenge study [Vaccine 19 (2001) 2273], a highly purified, heat-treated equine rabies immunoglobulin (pERIG HT, Favirab) did not elicit satisfactory protection. The efficacies of this batch, a second stage pERIG HT batch and reference RIG preparations (Imorab, Imogam Rage pasteurised, Berna antiserum) were compared in mice challenged with either Ariana canine field strain or CVS strain. Survival rates against Ariana challenge with the second pERIG HT batch were indistinguishable from those of other licensed preparations (83-90% survival), but the deficient batch did not provide satisfactory protection (53%). These data confirm the inadequate response to a first stage pERIG HT batch, but a current batch provides equivalent protection to that afforded by licensed HRIG and ERIG preparations.

Animals↗