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W Sommer

Publications and source records attributed to W Sommer.

At least 19 recordsLinked to original sources
PubMed2004

A cluster of differentially expressed signal transduction genes identified by microarray analysis in a rat genetic model of alcoholism.

Analyzing gene expression patterns in genetic models of alcoholism may uncover previously unknown susceptibility genes, and point to novel targets for drug development. Here, we compared expression profiles in alcohol-preferring AA rats with the alcohol-avoiding counterpart ANA line, and unselected Wistar rats. Cingulate cortex, Nc. accumbens, amygdala and hippocampus of each line were analyzed using the Afymetrix RN U34 arrays and dChip 1.1 software. Analysis of line-specific expression revealed 48 differentially expressed genes between AA and ANA rats. Elevated hippocampal neuropeptide Y (NPY) was found in ANA rats in agreement with previous studies. A cluster of MAP-kinases indicating altered signal transduction was upregulated within the Nc. Accumbens of the AA line, and is of particular functional interest. Within the amygdala, a more loosely inter-related cluster of cytoskeleton-associated genes may point to structural abnormalities. The observed dysregulations may contribute to the alcohol-preferring phenotype.

Alcoholism↗
PubMed2003

c-fos reduces corticosterone-mediated effects on neurotrophic factor expression in the rat hippocampal CA1 region.

The transcription of neurotrophic factors, i.e., basic fibroblast growth factor (bFGF) and brain-derived neurotrophic factor (BDNF) is regulated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation despite the lack of a classical glucocorticoid response element in their promoter region. A time course for corticosterone (10 mg/kg, s.c.) in adrenalectomized rats revealed a peak hormone effect at the 4 hr time interval for bFGF (110-204% increase), BDNF (53-67% decrease), GR (53-64% decrease), and MR (34-56% decrease) mRNA levels in all hippocampal subregions using in situ hybridization. c-fos mRNA levels were affected exclusively in the dentate gyrus after 50 min to 2 hr (38-46% decrease). Furthermore, it was evaluated whether corticosterone regulation of these genes depends on interactions with the transcription factor complex activator protein-1. c-fos antisense oligodeoxynucleotides were injected into the dorsal hippocampus of adrenalectomized rats. Corticosterone was given 2 hr later, and the effects on gene expression were measured 4 hr later. In CA1, antisense treatment significantly and selectively enhanced the hormone action on the expression of bFGF (44% enhanced increase) and BDNF (38% enhanced decrease) versus control oligodeoxynucleotide treatment. In addition, an upregulation of c-fos expression (89% increase) was found. There were no effects of c-fos antisense on hippocampal GR and MR expression. Thus it seems that a tonic c-fos mechanism exists within CA1, which reduces GR- and MR-mediated effects on expression of bFGF and BDNF.

Adrenalectomy↗
PubMed2002

Influences of presentation mode and time pressure on the utilisation of advance information in response preparation.

An important approach to the investigation of movement selection and preparation is the precuing paradigm where preliminary information about a multidimensional response leads to reaction time benefits which are positively related to the amount of precue information. This so-called precuing effect is commonly attributed to data-limited preparatory motoric processes performed in advance of the response signal. By means of recording the lateralised readiness potential (LRP), the present experiments investigated whether the precuing effect could be explained also by variables that affect strategic utilisation of stimulus-conveyed information. Experiment 1 presented fully and partially informative precues either in mixed or blocked mode. Experiment 2 exerted various degrees of time pressure to the different precue conditions. In both experiments, the precuing effect on reaction times and the LRP was fully preserved, refuting the notion that the sensitivity of the LRP to the amount of preliminary information merely reflects differential precue utilisation. As a major finding, time pressure increased the LRP amplitude during response preparation which is consistent with the view that response strategies generally influence movement preparation on a motoric level.

Adult↗
PubMed2002

Effects of tiagabine and diazepam on operant ethanol self-administration in the rat.

OBJECTIVE: Benzodiazepines (BDZ) are widely used in the treatment of anxiety and ethanol withdrawal. It has been suggested that this class of compounds may increase the reinforcing value of ethanol; however, the literature is scarce. Tiagabine has recently been introduced into clinical use as an anti-epileptic drug. It acts through inhibiting gamma-aminobutyric acid (GABA) reuptake, and thus represents a pharmacodynamically novel principle for potentiating GABAergic transmission. The objective of the present study was to examine whether these two manners of modulating GABAergic transmission would affect ethanol self-administration in rats. METHOD: Rats were trained on an operant oral ethanol self-administration task in a two-lever free-choice paradigm. When trained, subjects were treated with tiagabine (2, 6 and 18 mg/kg, intraperitoneally [i.p.]) or diazepam (0.5, 1.5 and 4.5 mg/kg, i.p.). Postsession blood alcohol concentrations and locomotor activity measures also were obtained. RESULTS: At nonsedating doses, neither tiagabine nor diazepam affected operant ethanol self-administration. At the highest doses (18 and 4.5 mg/kg, respectively), both drugs suppressed ethanol self-administration but also induced significant suppression of locomotion, indicative of sedation. CONCLUSIONS: Systemic administration of either the GABA-uptake blocker, tiagabine, or the GABA/BDZ agonist, diazepam, at nonsedating doses does not seem to affect oral ethanol self-administration.

Animals↗
PubMed2001

Induction of hippocampal glial cells expressing basic fibroblast growth factor RNA by corticosterone.

A transcriptional regulation of bFGF expression via both gluco- and mineralocorticoid receptors is known to exist. In the present study the glial nuclear fraction of bFGF transcripts was studied in sham-operated (SHAM), adrenalectomized (ADX), and corticosterone-treated ADX rats in subregions of the dorsal hippocampal formation. A substantial increase was observed in the population of bFGF RNA-expressing glial cells after acute corticosterone treatment (10 mg/kg, s.c.) in subregions of the CA1 area and the dentate gyrus but no changes were observed after adrenalectomy. The levels of glial nuclear bFGF transcripts were similar in all the experimental groups. These data suggest that in a subpopulation of hippocampal glial cells corticosterone regulates bFGF gene expression transcriptionally in an on/off manner.

Adrenalectomy↗
PubMed2001

Local 5,7-dihydroxytryptamine lesions of rat amygdala: release of punished drinking, unaffected plus-maze behavior and ethanol consumption.

Several serotonergic drugs are effective for anxiety disorders, but underlying mechanisms are unclear, and findings in experimental animals are difficult to reconcile with human data. It has been proposed that differential effects of serotonin within specific anatomical systems may account for these difficulties, and the amygdala has been suggested as one of the structures involved. To examine this hypothesis, the neurotoxin 5,7-dihydroxytryptamine was administered locally in rat amygdala. Within the amygdala, serotonin was depleted by approximately 80%, with other transmitters unaffected, and serotonin transporter labelling was decreased by approximately 85%. Cortical areas near the lesion site were also affected, although to a lesser degree. Other forebrain areas were unaffected. Lesions resulted in a specific anti-conflict effect in a punished drinking test, but did not influence elevated plus-maze behavior (under baseline conditions and after restraint stress), locomotor activity or ethanol intake. These data suggest that the punished drinking test and the elevated plus-maze may activate different components of fear circuitry, and that the serotonergic input to the amygdala specifically participates in fear-related behavioral suppression mediated by this structure.

5,7-Dihydroxytryptamine↗
PubMed2001

Differential expression of diacylglycerol kinase iota and L18A mRNAs in the brains of alcohol-preferring AA and alcohol-avoiding ANA rats.

Ethanol preference and behavioral disinhibition in AA (alcohol accepting) animals is a behavioral constellation similar to that seen in human type II alcoholism, for which considerable genetic loading has been shown. In search of novel neural substrates for this phenotype, we compared gene expression in the cerebral cortex of the AA rat with two groups of control animals, the ANA (alcohol non-accepting) line and heterogeneous Wistar animals, by differential display RT-PCR. We identified two transcripts, ribosomal protein L18a mRNA and diacyglycerol kinase iota mRNA, which are differentially expressed between AA and ANA rats. Ribosomal protein L18A mRNA is evenly expressed throughout the brain, but strongly reduced in cortex of AA rats vs controls. Diacylglycerol kinase iota is exclusively found in the brain, and expressed in a distinct regional pattern. Its cortical expression is about 25% higher in AA than ANA rats. Differential display RT-PCR seems to provide a feasible strategy to identify previously unknown genes whose differential expression correlates with behavioral phenotypes related to dependence.

Alcohol Drinking↗
PubMed2001

Multiple bottlenecks in information processing? An electrophysiological examination.

When two stimuli are to be processed in rapid succession, reaction time (RT) to the second stimulus is delayed. The slowing of RT has been attributed to a single processing bottleneck at response selection (RS) or to a central bottleneck following the initiation of the first response. The hypothesis of a response initiation bottleneck is mainly based on reports of underadditive interactions between stimulus onset asynchrony (SOA) and the number of stimulus-response alternatives (simple vs. two-choice response). The present study tested the hypothesis of a response initiation bottleneck by recording the lateralized readiness potential (LRP), a brain wave, emerging during or immediately following RS. The LRP findings were consistent with a central bottleneck but did not support the late bottleneck hypothesis. Instead, the LRP provided direct evidence that the underadditive interaction of number of alternatives and SOA is due to an increase of response anticipations in the simple response condition.

Adult↗
PubMed2001

Sequence-sensitive subcomponents of P300: topographical analyses and dipole source localization.

P300 amplitude and reaction time (RT) are strongly affected by the sequence of events preceding the eliciting stimulus. Sommer, Leuthold and Soetens (1999) found that robust sequential effects in P300 amplitude could be dissociated from more variable sequential effects in RTs. However, global changes in P300 amplitude and topography gave rise to the suggestion that sequential effects are specific for a subcomponent of P300 that is separate from and anterior to the classical parietal P300. Here, confirming evidence for dissociable subcomponents of P300 is reported from two experiments. Independent component analysis separated a centrally distributed sequence-sensitive subcomponent from a more parietal subcomponent. Subsequent dipole source analysis indicated a deep mesial source for the sequence-sensitive subcomponent. Overlap with reafferent somatosensory activity appears to be responsible for an apparent lateralization of this component towards the hemisphere ipsilateral to the responding hand.

Adolescent↗
PubMed2001

Differential expression of NPY and its receptors in alcohol-preferring AA and alcohol-avoiding ANA rats.

BACKGROUND: Central neuropeptide Y (NPY) is known to control feeding and stress responses. Recently, it has been suggested that NPY also has a role in regulation of alcohol consumption. METHODS: NPY and NPY receptor expression in genetically selected alcohol-preferring (AA), alcohol-nonpreferring (ANA), and Wistar rats were investigated. Expression was assessed using in situ hybridization histochemistry with riboprobes specific for preproNPY, Y1, and Y2 receptors. Effects of central NPY administration on ethanol self-administration were also examined in AA, ANA, and Wistar rats by using oral operant self-administration. RESULTS: NPY mRNA expression was higher in ANA than in both AA and Wistar rats in the hippocampal CA region and dentate gyrus, whereas AA and Wistar did not differ from each other. No differences in NPY expression were found in the other regions analyzed: cingulate cortex, medial nucleus of the amygdala, arcuate, and paraventricular nuclei of the hypothalamus. Y1 receptor mRNA expression did not differ between the three lines. Y2 expression was higher in the dentate gyrus of both AA and ANA rats than in Wistar subjects. In the medial amygdala, Y2 mRNA was reduced in the AA line, compared to both ANA and Wistar rats. NPY injected intracerebroventricularly (1.5-3.0 nmol) did not affect operant ethanol self-administration in any of the three lines examined. CONCLUSION: The NPY system seems to differ in several respects between rat lines with different levels of alcohol preference. Differences observed within the hippocampus could be related to behavioral traits other than alcohol intake but it is also possible that elevated hippocampal expression of NPY in the ANA rats contributes to the low alcohol intake of this line. Aberrant NPY expression and/function within the amygdala complex could contribute to alcohol preference and constitute an anatomic substrate of the effects of NPY expression on alcohol intake observed previously in genetically modified animals.

Alcohol Drinking↗
PubMed2000

Gluco- and mineralocorticoid receptor-mediated regulation of neurotrophic factor gene expression in the dorsal hippocampus and the neocortex of the rat.

Gluco- and mineralocorticoid receptors (GR and MR) act via common promoter elements but may exert different effects on gene regulation in various regions of the forebrain. In order to separately analyse the role of GR and MR in the regulation of neurotrophic factor genes and their receptors, we used adrenalectomy and subsequent hormone injections in the rat as a model system. Twenty-four hours after adrenalectomy rats were injected with a single dose of corticosterone (2 and 10 mg/kg), aldosterone (0.5 mg/kg) or the synthetic glucocorticoid agonist RU 28362 (4 mg/kg). Gene expression of basic fibroblast growth factor (bFGF) and its high-affinity receptors [fibroblast growth factor receptor subtypes 1-3 (FGF-R1, FGF-R2, FGF-R3)], as well as brain-derived growth factor (BDNF) and neurotrophin-3 (NT-3) was analysed at 4 h after the hormone injection in CA1-CA4 (cornus of Ammon areas of the hippocampus) and dentate gyrus of the dorsal hippocampus and in neocortex by means of in situ hybridization. We found that bFGF is regulated in CA2, CA3 and dentate gyrus by GR and MR together, and in CA1, CA4 and neocortex by GR alone. FGF-R2 expression in the hippocampus seems to be regulated only by MR, while BDNF expression appears to depend on both receptors. FGF-R1, FGF-R3 and NT-3 were only moderately affected by the hormone activation of GR and MR acting in concert or alone in the various regions. Thus, the present findings suggest that the adrenal cortical system through GR and MR participate in the control of neurotrophic factor signalling in a highly subregion- and cellular-dependent manner.

Adrenalectomy↗
PubMed2000

Site-specific administration of antisense oligonucleotides using biodegradable polymer microspheres provides sustained delivery and improved subcellular biodistribution in the neostriatum of the rat brain.

Antisense oligonucleotides (ODNs) are being increasingly used in the central nervous system as biological tools, as drug-target validation agents and as potential therapeutic agents. Although the local delivery of naked ODNs to the brain can result in the desired biological effects, the duration of efficacy is relatively short lived due to the combined effects of rapid ODN degradation and elimination half-lives in vivo. In this study, we have examined the use of biodegradable polymer microspheres as a site-specific delivery system for targeting ODNs to the neostriatum of the rat brain. Model phosphorothioate backbone-modified ODNs were entrapped within poly(D,L-lactide-co-glycolide) (PLAGA) microspheres using a double emulsion-deposition method and the formulations characterised in terms of particle size, surface morphology, percent encapsulation efficiency, ODN loading and in vitro release profiles. For in vivo evaluation, PLAGA microspheres containing fluorescently-labelled ODNs were stereo-taxically administered to the neostriatum of the rat brain and biodistribution of ODNs monitored after 48 h. Administration of free fluorescently-labelled ODNs to the neostriatum resulted in a punctate cellular distribution of ODNs after 24 h with little or no ODN remaining in the neostriatum after 48 h. In comparison, fluorescently-labelled ODNs delivered using polymer microspheres were intensely visible in cells after 48 h post-administration and the fluorescence appeared to be diffuse covering both cytosolic and nuclear regions. Dual-label immunohistochemical analyses suggested that ODNs were mainly distributed to neuronal cells. These data indicate that site-specific administration of ODNs using biodegradable polymer microspheres will not only provide sustained delivery of nucleic acids but can also improve the cellular distribution of ODNs to brain cells. Sustained or controlled-release biodegradable polymer formulations, therefore, represent an attractive strategy for improved local delivery of ODNs to the CNS.

Animals↗
PubMed1999

[Antisense oligonucleotides are clinically tested. They inhibit the expression of disease-related genes].

Recent advances in molecular biology have improved our understanding of basic pathophysiological mechanisms, and indicated possible strategies for their manipulation. The use of oligonucleotides occupies a prominent position among the emerging strategies, and has given rise to a new generation of pharmaceutical preparations now entering clinical usage. Antisense oligonucleotides are capable of blocking the expression of specific genes, thus permitting highly precise intervention in pathophysiology at the molecular level. Several clinical trials have recently produced highly promising results. The most likely applications of antisense agents are viral infections, malignancies, and chronic inflammatory disease. The article consists in a presentation of the antisense principle, discussion of its advantages and limitations, and a review of recent clinical developments and future prospects.

Cell Transformation, Neoplastic↗
PubMed1999

Anxiogenic-like action of galanin after intra-amygdala administration in the rat.

The neuropeptide galanin is expressed in brain structures implicated in regulation of emotionality. The amygdala is known to play a central role in mechanisms of fear and anxiety. We therefore examined the effects of galanin (0.2 and 0.6 nmol/side) on experimental anxiety upon microinjection into the amygdala. Two established animal models of anxiety were used: a punished drinking test, and the elevated plus-maze. Punished responding was dose dependently suppressed by intra-amygdala galanin, whereas unpunished responding, drinking motivation, locomotor activity, and shock thresholds were unaffected. No effects on experimental anxiety were seen in the plus-maze following galanin injection. When injected into parietal cortex, no anxiety promoting properties of galanin were detected. These data suggest that activation of galanin receptors in amygdala modulates neurotransmission involved in fear and experimental anxiety.

Amygdala↗
PubMed1999

ERP correlates of error processing in spatial S-R compatibility tasks.

When participants in reaction time (RT) tasks commit errors, the event-related brain potential (ERP) has been reported to show a negative-going deflection, the so-called error negativity (NE), followed by a positive-going component (PE). To examine the locus of NE within information processing and in order to test whether two successive P300 components are elicited in error trials, we manipulated the duration of perception- and response-related processing stages in visual and auditory spatial S-R compatibility tasks. Our results suggest that NE is closely coupled to motoric processes and elicited when information about the incorrectly executed response is available. The latency of the subsequent PE was influenced by perceptual as well as by response-related variables. Its scalp topography was not different from that of the P300 in correct trials and from a preceding positivity in incorrect trials. Therefore, we concluded that an additional error-related P300 is elicited by error events presumably relating to error recognition and the updating of the error context.

Acoustic Stimulation↗
PubMed1999

Covert signs of expectancy in serial reaction time tasks revealed by event-related potentials.

Choice reaction time is strongly determined by the sequence of preceding stimuli. With long response-stimulus intervals (RSIs), a cost-benefit pattern is observed, which has been related to expectancy, whereas with short RSIs a benefit-only pattern emerges, possibly because of automatic facilitation. In the present study, event-related potentials were recorded while subjects performed serial choice responses to visual and auditory stimuli at long and short RSIs. As expected, reaction times displayed cost-benefit and benefit-only patterns at long and short RSIs, respectively. In contrast, sequential effects in event-related potential amplitudes displayed a cost-benefit pattern, unaffected by the RSI. The results demonstrate that an expectancy-like mechanism is always active in serial tasks but appears to influence performance only when the RSI is long.

Adult↗
PubMed1999

[Education of patients with inflammatory bowel diseases].

Patients with chronic inflammatory bowel disease were interviewed about their degree of satisfaction with the medical information provided by the professional staff and the reasons for their satisfaction. 30 patients, suffering from ulcerative colitis or Crohn's disease, underwent semistandardized interviews with the result that professional education about their disease was provided either in a single concluding session or in several consecutive sessions. The patients were informed about the diagnosis, the assumed etiology and medical treatment, yet much less frequently were they told about the course of their disease or its possible consequences. On the average the clarifying sessions did not take more than 10 to 15 minutes. Only 50% of the patients were able to fully understand the information they received. 40% were dissatisfied. Greater patient satisfaction was related to more time, more detailed explanation, and emotional support by the physician. These facts should be seriously considered during medical training.

Adult↗