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PubMedDate not supplied

Differential effects of selective opioid peptide antagonists on the acquisition of pavlovian fear conditioning.

Pretreatment with opioid antagonists enhances acquisition of Pavlovian fear conditioning. The present experiments attempted to characterize the type of opioid receptor responsible for this effect using a procedure that assessed the fear of rats to a chamber previously associated with electric shock (1 mA, 0.75 s). Freezing, a species-typical immobility, was employed as an index of fear. Two mu opioid antagonists, CTOP (40 ng) and naloxonazine (10 micrograms), enhanced conditioning. On the other hand, the kappa antagonist nor-binaltorphimine reduced conditioning. Two delta antagonist treatments (16-methyl cyprenorphine and naltrindole) had no reliable effect on acquisition. Thus the enhancement of conditioning appears to be mediated by mu receptors. Previous research has shown that the conditional fear produced by these procedures caused an analgesia that is also mediated by mu receptors. It is argued that the enhancement effect occurs because of an antagonism of this analgesia and that the analgesia normally acts to regulate the level of fear conditioning.

Animals↗
PubMed1983

Differential sensitivity of selected brain areas to excitatory amino acids.

The 22Na+ efflux stimulated by selected agonists of the 4 excitatory amino acid receptors, previously detected in the striatum, has been studied on 22Na+-preloaded slices prepared from 10 major areas of the rat brain. All brain areas were found to be sensitive, albeit to varying extents, to excitatory amino acids. The cerebellum was exceptional in its high sensitivity to kainate and quisqualate and in the absence of effect of N-methyl-D-aspartate. These results support the suggestion that excitatory amino acids interact with heteregenous receptors which differ from each other not only in their pharmacological properties but also in their regional distribution.

Amino Acids↗
PubMed1984

Differential sensitivity of selected rat brain areas to excitatory neurotransmitters released by K+ depolarization.

The depolarization of brain slices by high K+ concentrations in the presence of Ca2+ ions leads to the release from nerve terminals of endogenous excitatory neurotransmitters that interact with subsynaptic receptors controlling the neuronal membrane permeability to Na+ ions. This interaction has been studied by following the K+-evoked Ca2+-dependent 22Na+ efflux from 22Na+-preloaded slices from the cortex, striatum, hippocampus, cerebellum, substantia nigra and hypothalamus of the rat. The results indicate that the so-called N-methyl-D-aspartate receptor mediates the bulk of the excitatory transactions in the cortex and striatum whereas a subsynaptic glutamate receptor may mediate those in the hippocampus and cerebellum.

Animals↗
PubMed2003

Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity.

It is becoming increasingly apparent that multiple functions of the frontal cortex such as inhibitory control and executive attention are likely sustained by its functionally distinct and interacting sub-regions but the precise localization of dissociable executive processes has proved difficult and controversial. In the present series of studies, we investigated the behavioural effects of bilateral excitotoxic lesions of different regions of the rat neocortex in the 5-choice serial reaction time task. Whereas lesions of the dorsal anterior cingulate cortex (ACC) impaired performance of the task as revealed by a reduction in discriminative accuracy, lesions made to distinct ventral regions of the frontal cortex showed selective deficits in inhibitory measures of control. Specifically, the infralimbic lesion produced increases in premature responding that was accompanied by fast response latencies. By comparison, the orbitofrontal lesion showed perseverative tendencies particularly when the inter-trial interval was made long and unpredictable, a challenge that would normally promote premature responding instead. These different behavioural effects following dorsal and ventral lesions of the rodent frontal cortex signifies the integrity of the frontal cortex in multiple executive mechanisms that work independently and complementarily by which performance is optimized. Furthermore, these data provide new insights into the functional organization of the rodent frontal cortex with a particular emphasis on localization of function.

Animals↗
PubMed2006

Differential effects of selective and non-selective inhibition of nitric oxide synthase on the expression and activity of cyclooxygenase-2 during gastric ulcer healing.

Nitric oxide synthases (NOS) and cyclooxygenase-2 (COX-2) are important enzymes involved in ulcer healing but interactions between them have not been clearly defined. The aim of this study was to investigate the effects of selective or non-selective inhibition of NOS on the expression and activity of COX-2 during healing of acetic acid-induced gastric ulcers in rats. N-[3-(aminomethyl)benzyl] acetamidine (1400 W), a potent selective inhibitor of inducible nitric oxide synthase (iNOS), at a dose of 0.1 mg/kg/day, was found to reduce the ulcer sizes at day 3 and 7 post-ulcer induction. On the other hand, 15 mg/kg/day of NG-nitro-L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor that suppresses both iNOS and endothelial nitric oxide synthase (eNOS), enlarged the ulcer sizes over the same time periods. The expression of COX-2 and COX activity, together with NF-kappaB activation in the ulcer tissues were down-regulated by L-NAME but not 1400 W. It is concluded that iNOS may contribute to ulcer formation while COX-2 and eNOS promote ulcer healing. eNOS enhances COX-2 expression possibly through the activation of NF-kappaB.

Acetic Acid↗
PubMed2007

Characterization of early retinal progenitor microenvironment: presence of activities selective for the differentiation of retinal ganglion cells and maintenance of progenitors.

The maintenance and differentiation of retinal progenitors take place in the context of the microenvironment in which they reside at a given time during retinal histogenesis. To understand the nature of the microenvironment in the developing retina, we have examined the influence of activities present during the early stage of retinal histogenesis on enriched retinal progenitors, using the neurosphere model. Early and late retinal progenitors, enriched as neurospheres from embryonic day 14 (E14) and E18 rat retina, respectively, were cultured in embryonic day 3 (E3) chick retinal conditioned medium, simulating the microenvironment present during early retinal histogenesis. Examination of the differentiation and proliferation of retinal progenitors revealed that the early microenvironment contains at least three regulatory activities, which are partitioned in different size fractions of the conditioned medium with different heat sensitivity. First, it is characterized by activities, present in heat stable <30 kDa fraction, that promote the differentiation of retinal ganglion cells (RGCs), the early born neurons. Second, it contains activities, present in heat-sensitive >30 kDa fraction, that regulate the number of early born neurons and maintain the pool of retinal progenitors. Third, it possesses activities, present in heat-sensitive <30 kDa fraction, that prevent the premature differentiation of early retinal progenitors into the late born neurons. Thus, our observations demonstrate the regulatory influence of microenvironment on the maintenance and differentiation of retinal progenitors and establish neurospheres as a viable model system for the examination of such influences.

Animals↗
PubMed1998

Differential effects of selective adenosine A1 and A2A receptor agonists on dopamine receptor agonist-induced behavioural responses in rats.

The effects of the systemic (i.p.) administration of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) and the selective adenosine A2A receptor agonist sodium 2-p-carboxyethyl)phenylamino-5'-N-carboxamidoadenosine (CGS 21680) on different dopamine receptor agonist-induced behaviours were studied in the male rat. CGS 21680 (1 micromol/kg), but not CPA, was found to counteract the stereotypies induced by the non-selective dopamine receptor agonist apomorphine (0.25 mg/kg s.c.). Low doses of CGS 21680 (0.1 micromol/kg) and high doses of CPA (3 micromol/kg) counteracted yawning induced by the dopamine D2 selective agonist quinpirole (0.05 mg/kg). On the other hand, low doses of CPA (0.3 micromol/kg) antagonized grooming induced by the selective dopamine D1 receptor-selective agonist SKF 38393 (10 mg/kg i.p.), while CGS 21680 was ineffective. These results are consistent with the proposed existence of a selective antagonistic modulation of dopamine D1 and D2 receptors by adenosine A1 and A2A receptors, respectively. The ability of CGS 21680 to counteract apomorphine-induced stereotypies is weaker compared to its previously reported antagonistic effect of amphetamine-induced motor activity. This supports the hypothesis that adenosine A2A receptor agonists may be potential antipsychotic drugs with a low potential for extrapyramidal side effects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2002

Multivariate approach for selecting sets of differentially expressed genes.

An important problem addressed using cDNA microarray data is the detection of genes differentially expressed in two tissues of interest. Currently used approaches ignore the multidimensional structure of the data. However it is well known that correlation among covariates can enhance the ability to detect less pronounced differences. We use the Mahalanobis distance between vectors of gene expressions as a criterion for simultaneously comparing a set of genes and develop an algorithm for maximizing it. To overcome the problem of instability of covariance matrices we propose a new method of combining data from small-scale random search experiments. We show that by utilizing the correlation structure the multivariate method, in addition to the genes found by the one-dimensional criteria, finds genes whose differential expression is not detectable marginally.

Algorithms↗
PubMed1997

Discriminative stimulus properties of ethanol in the rat: differential effects of selective and nonselective benzodiazepine receptor agonists.

Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall response rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat.

Animals↗
PubMed1998

Differential effect of selective cyclooxygenase-2 (COX-2) inhibitor NS 398 and diclofenac on formalin-induced nociception in the rat.

Prostaglandins (PGs) are known to be involved in inflammatory and nociceptive processing. Since the discovery of at least two isozymes of cyclooxygenase (COX), inhibition of COX-2 has been suggested to be responsible for the therapeutic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). In the present study, the effects of a rather selective COX-2 inhibitor, NS-398 (0.3-27 mg/kg i.p.), were studied using the rat formalin test as a model of acute nociception. Diclofenac (non-selective COX inhibitor; 0.3-27 mg/kg i.p.) was used as a control. NS-398 revealed antinociceptive activity only at a dose (27 mg/kg) which results in plasma concentrations which most likely do not selectively inhibit COX-2. By contrast, diclofenac inhibited formalin-induced flinching behaviour over the whole dose range tested. Our results suggest that PGs mediating nociception in the formalin test of the rat are most likely produced via the COX-1 as well as COX-2 pathways. Thus, in an acute model of nociception a non-selective COX inhibitor may offer advantages as compared to a selective COX-2 inhibitor.

Animals↗
PubMed2000

Application of a method incorporating differential centrifugation for selective isolation of motile actinomycetes in soil and plant litter.

The present paper describes a simple enrichment technique which enables rapid and selective isolation of diverse zoosporic actinomycete genera directly from soil and plant litter. This technique, designated the rehydration and centrifugation (RC) method, consists of immersing the air-dried source material in 10 mM phosphate buffer containing 10% soil extract, letting the preparation stand at 30 degrees C for 90 min, followed by centrifugation of the fluid at 1,500 x g for 20 min. Portions of the supernatant containing actinomycete zoospores are plated on the humic acid-vitamin agar which is supplemented with nalidixic acid and trimethoprim as the selective inhibitors for Gram-negative bacteria and bacilli. The phosphate buffer-soil extract solution significantly promoted liberation of motile zoospores from the source material. The centrifugation stage greatly eliminated streptomycetes and other non-motile actinomycetes from the liquid phase, thereby facilitating selective growth of rare, motile actinomycetes on the isolation plates subsequent to inoculation. Ten different soil and leaf-litter samples, taken from fields, forests, and stream banks, were examined. The RC method consistently achieved preferential isolation of motile actinomycetes in all samples, which accounted for 37-86% of the total microbial population recovered. The most frequently isolated motile actinomycetes were Actinoplanes and Dactylosporangium. Strains of Actinokineospora, Catenuloplanes and Kineosporia were also recovered, depending on the nature of the samples examined. Other motile actinomycetes that were occasionally isolated in small numbers included Actinosynnema, Geodermatophilus and Sporichthya.

Actinomycetales↗
PubMed1996

Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.

The effect of injection into the medial septum of a toxin selective for cholinergic neurons, 192 IgG-saporin, was examined in rats trained to perform 2 versions of the radial 8-arm maze task. Rats were first trained to perform a task with varying delays (0, 1, 2 min) imposed between the 4th correct arm choice and access to all 8 arms. Lesioned rats made significantly more errors in the first 4 choices compared with controls and significantly more errors after delays; however, this effect was not delay dependent. Rats were then trained on a different version of this 8-arm maze task in which they learned to avoid 2 arms that were never baited. There was no treatment effect on acquisition of this task. These data are consistent with the hypothesis that the cholinergic projection to the hippocampus facilitates the acquisition of information into the system responsible for short-term memory for locations visited (spatial working memory) but is not involved in retention of this information. It also appears to play no role in either the acquisition or retention of place-nonreward associations (spatial reference memory).

Animals↗
PubMed2003

Discriminative validity of selected measures for differentiating normal from aphasic performance.

Normal elderly and mildly aphasic individuals may exhibit similar impairments in comprehension and expression. The discriminative validity between normal and aphasic performance on most standardized measures of aphasia has not been reported. The authors compared the performance of 18 aphasic and 18 normal adults to determine the discriminative validity of 2 general language measures--the Porch Index of Communicative Ability (B. E. Porch, 1967) and the Western Aphasia Battery (A. Kertesz, 1982)--and 2 functional communication measures--the Communication Activities of Daily Living-Second Edition (A. L. Holland, C. Frattali, and D. Fromm, 1999) and the American Speech-Language-Hearing Association's Functional Assessment of Communication Skills for Adults (C. Frattali, C. K. Thompson, A. L. Holland, C. B. Wohl, and M. K. Ferketic, 1995). All between-groups comparisons of summary scores for each measure showed significant mean differences. Expressive language ability and efficiency of performance best differentiated between the aphasic and normal groups. However, group performance ranges overlapped by at least 10% on each measure. To enhance the differential diagnosis of aphasia, supplementing formal test results with additional subjective and objective evidence is recommended.

Adult↗
PubMed2002

Differential effects of selective and non-selective NOS inhibition on renal arginine and protein metabolism during endotoxemia in rats.

BACKGROUND AND AIMS: The kidney is the main endogenous producer of circulating arginine. Renal arginine disposal is directed to protein synthesis, urea production and nitric oxide synthesis. The administration of nitric oxide synthase inhibitors during sepsis may be beneficial or detrimental depending on the specificity of the inhibitor. We aimed to measure the effects of two NOS inhibitors, with different specificity, on renal arginine and protein turnover in a rat model of sepsis. METHODS: Rats were subject to double hit endotoxemia and either L-NAME (non-specific), SMT (iNOS specific) or saline. Under anesthesia, vessels supplying and draining the kidney were catheterized. Systemic and intra-renal arginine and protein metabolism were measured using a primed continuous infusion of L-[2,3-(3)H]arginine and L-[2,6-(3)H]phenylalanine. RESULTS: Non-specific NOS reduced systemic protein and arginine turnover, whereas selective iNOS inhibition did not. In the kidney, blood flow was reduced by L-NAME, but not by SMT. In conjunction with this, non-selective NOS inhibition increased renal protein breakdown, whereas selective iNOS inhibition increased renal arginine production. CONCLUSIONS: This study shows that non-selective NOS inhibition using L-NAME is detrimental for systemic and renal protein metabolism. Selective NOS inhibition stimulates renal arginine synthesis, without changing circulating arginine levels.

Animals↗
PubMed1996

Differential fatty acid selection during biosynthetic S-acylation of a transmembrane protein (HEF) and other proteins in insect cells (Sf9) and in mammalian cells (CV1).

The transmembrane glycoprotein HEF and its acylation deficient mutant M1 were expressed in Sf9 insect cells infected with recombinant baculovirus and in CV1 mammalian cells using the vaccinia T7 system. In insect cells (Sf9), both wild type HEF and HEF(M1) are synthesized in their precursor form HEF0, which appears as a double band in SDS gels. Digestion with glycopeptidase F and endoglycosidase H reveals that the larger 84-kDa form is modified by the attachment of unprocessed carbohydrates of the high mannose type whereas the smaller 76-kDa form is non-glycosylated. As revealed by in vitro labeling experiments with palmitic acid another modification of HEF is the attachment of a long chain fatty acid to cysteine residue Cys-652 which is located at the internal border of the cytoplasmic membrane. After labeling with [3H]palmitic acid in both systems only HEF(WT) is acylated, whereas HEF(M1) is not. High performance liquid chromatography analysis of the fatty acids bound to HEF(WT) expressed in Sf9 insect cells reveals nearly 80% of palmitic acid. In contrast to this finding, the acylation pattern of HEF expressed in CV1 cells shows nearly the same amounts of stearic and palmitic acid (40%). Since the interconversion of the input [3H]palmitic acid to stearic acid is even lower in CV1 cells than in insect cells, it follows that only HEF expressed in mammalian, but not in insect cells selects for stearic acid during its biosynthetic acylation. We extended our study to acylation of endogenous proteins in Sf9 cells. In finding only palmitate linked to protein we present evidence that, in contrast to mammalian cells, insect cells (Sf9) cannot transfer stearic acid to polypeptide. This finding favors the hypothesis of enzymatic acylation over non-enzymatic mechanisms of acyl transfer to protein.

Acylation↗
PubMed1982

Selective emergence of differentiated chondrocytes during serum-free culture of cells derived from fetal rat calvaria.

Cells dispersed from the chondrocranial portions of fetal rat calvaria proliferated and performed specialized functions during primary culture in a chemically defined medium. Mature cultures were typified by multilayered clusters of redifferentiating cartilage cells. Flattened cells that lacked distinguishing features occupied areas between the clusters. Alkaline phosphate-enriched, ultrastructurally typical chondrocytes within the clusters were encased in a dense extracellular matrix that stained prominently for chondroitin sulfate proteoglycans. This matrix contained fibrils measuring 19 nm in diameter, which were associated with proteoglycan granules that preferentially bound ruthenium red. A progressive increase in the number of cells indicated the proliferation of certain elements in the primary culture. The cells in primary culture were biochemically as well as morphologically heterogeneous since they were found to synthesize type I and type II collagens. Homogeneous populations of redifferentiated chondrocytes were recovered as floating cells and were shown to express the chondrocyte phenotype in secondary culture. Subcultured cells synthesized type II collagen and its precursors almost exclusively and incorporated 35SO4 into proteoglycan monomer and aggregates to a greater degree than the cells in primary culture. The pattern of proteoglycan monomer and aggregate labeling resembled that of intact cartilage segments and bovine articular chondrocytes. Skin fibroblasts harvested from the same rat fetuses failed to proliferate when maintained under identical conditions. Hence, exogenous hormones, growth factors, and protein are not required for chondrocyte growth and maturation.

Animals↗