58 research outputs found
Does fear remain in Old Testament ×ר×ת ××××?
Es gibt unter Gelehrten viele verschiedene Ansichten Ăźber die Bedeutung von Gottesfurcht im AT, und diese verschiedenen Ansichten finden ihren Ausdruck in den verschiedenen Ăbersetzungen des Begriffs in den vielen Bibelversionen. Viele meinen, das Wesen der Gottesfurcht verändere sich in dem Grad, in dem sich die Religion Israels veränderte. Diese vorliegende Arbeit geht davon aus, dass die Gottesfurcht, wie sie im Alten Testament verwendet wird, näher mit der Emotion (der Furcht) verbunden ist, als viele Vertreter der historisch-kritischen Schule glauben mĂśchten. Während der Begriff zeitweise zur Beschreibung des Phänomens Religion (z.B. Ehrfurcht, Ehre, Anbetung, usw.) herangezogen wird, liegt die Hauptbedeutung des besprochenen Phänomens darin, dass man sich fĂźrchtet. Um diese Theorie zu untermauern, mĂźssen einige Werke, die die Geschichte Israels zu rekonstruieren versuchen, hinterfragt werden â allen voran die einflussreiche formkritische Studie Gottesfurcht im Alten Testament von Joachim Becker. Die Arbeit geht davon aus, dass die Argumente Beckers fĂźr seine These, der Begriff Gottesfurcht habe sich in seiner Bedeutung geändert, keine befriedigende Antwort geben. Die Texte, die fĂźr die Betrachtung der Gottesfurcht in Frage kommen, sind in ihrem biblischen Kontext zu sehen (was historisch-kritische Betrachtungen nicht immer gemacht haben) und von einem konservativen hermeneutischen Blickwinkel zu deuten. Der semantische Befund zur Gottesfurcht ist ziemlich konstant im gesamten AT (und ebenso im NT) und ist von zwei Kategorien gekennzeichnet: Die âEreignisâ- (âEventâ-) Gottesfurcht (d.h. Narrative, in denen Akteure sich vor einem Furcht einflĂśĂendem Objekt ängstigen) zeigt, dass âFurchtâ (normalerweise ×ר×) mit der Emotion Furcht verbunden ist, während die âTugendâ- (âVirtueâ-) Gottesfurcht (wo die Gottesfurcht als Tugend begriffen wird, z.B. in Ps 103:11 [âDenn so hoch der Himmel Ăźber der Erde ist, läĂt er seine Gnade walten Ăźber die, so ihn fĂźrchtenâ]) mehr abstrakte Bedeutungen haben kann, aber nie auf die Emotion Furcht verzichtet. Ein genauer Blick auf die Texte im Buch Prediger soll helfen, diese These zu untermauern.Scholars have many different views about what OT fear-of-God means, and these different views are reflected in the various translations of the expression in the many Bible versions. The variety of opinions is to a large extent a product of the understanding that the concept evolved as Israelâs religion evolved. The present work takes the position that the OT fear-of-God idea remains closer to the fear emotion/feeling than many critical-era scholars have allowed. While the expression may be used from time to time to signify the more refined elements of faith (e.g., reverence, awe, honor, worship), it is likely that the semantic center remains on the fear emotion/feeling. To build a case for this, several works that assume a critical reconstruction of Israelâs history are challengedâespecially the influential form-critical work of Joachim Becker (Gottesfurcht im Alten Testament); the evidence that Becker musters to make the case that the fear-of-God concept evolved is argued to be insufficient. The OT fear-of-God texts in their biblical contexts (opposed to critically-reconstructed contexts) are then analyzed from a conservative hermeneutical starting point, and the case is made that the semantic range of fear-of-God remains quite stable throughout the OT (and throughout the NT as well): âeventâ fear-of-God cases (i.e., narrative events that depict people fearing before a fear-evoking object) demonstrate that âfearâ (usually ×ר×) is semantically centered on the emotion/feeling of fear; âvirtueâ fear-of-God cases (i.e., cases in which fear-of-God is understood as a virtue [e.g., âFor as the heavens are high above the earth, so great is his steadfast love toward those who fear himâ Ps 103:11]) appear at times to connote the more abstract phenomena associated with Israelâs worship, yet never fail to denote the phenomenon of being afraid. An especially close look at the fear-of-God texts of Ecclesiastes will help to demonstrate this
Nicotinic receptor modulation to treat alcohol and drug dependence
Alcohol and drug dependence are serious public health problems worldwide. The prevalence of alcohol and drug dependence in the United States and other parts of the world is significant. Given the limitations in the efficacy of current pharmacotherapies to treat these disorders, research in developing alternative pharmacotherapies continues. Preclinical and clinical evidence thus far has indicated that brain nicotinic acetylcholine receptors (nAChRs) are important pharmacological targets for the development of medications to treat alcohol and drug dependence. The nAChRs are a super family of ligand gated ion channels, and are expressed throughout the brain with twelve neuronal nAChR subunits (Îą2âÎą10 and β2âβ4) identified. Here, we review preclinical and clinical evidence involving a number of nAChR ligands that target different nAChR subtypes in alcohol and nicotine addiction. The important ligands include cytisine, lobeline, mecamylamine, varenicline, sazetidine A and others that target Îą4β2* nAChR subtypes as small molecule modulators of the brain nicotinic cholinergic system are also discussed. Taken together, both preclinical and clinical data exist that support nAChRâbased ligands as promising therapeutic agents for the treatment of alcohol and drug dependence
Polysubstance addiction vulnerability in mental illness: Concurrent alcohol and nicotine selfâadministration in the neurodevelopmental hippocampal lesion rat model of schizophrenia
Multiple addictions frequently occur in patients with mental illness. However, basic research on the brainâbased linkages between these comorbidities is extremely limited. Toward characterizing the first animal modeling of polysubstance use and addiction vulnerability in schizophrenia, adolescent rats with neonatal ventral hippocampal lesions (NVHLs) and controls had 19 weekdays of 1 hour/day free access to alcohol/sucrose solutions (fading from 10% sucrose to 10% alcohol/2% sucrose on day 10) during postnatal days (PD 35â60). Starting in adulthood (PD 63), rats acquired lever pressing for concurrent oral alcohol (10% with 2% sucrose) and iv nicotine (0.015 mg/kg/injection) across 15 sessions. Subsequently, 10 operant extinction sessions and 3 reinstatement sessions examined drug seeking upon withholding of nicotine, then both nicotine and alcohol, then reintroduction. Adolescent alcohol consumption did not differ between NVHLs and controls. However, in adulthood, NVHLs showed increased lever pressing at alcohol and nicotine levers that progressed more strongly at the nicotine lever, even as most pressing by both groups was at the alcohol lever. In extinction, both groups showed expected declines in effort as drugs were withheld, but NVHLs persisted with greater pressing at both alcohol and nicotine levers. In reinstatement, alcohol reaccess increased pressing, with NVHLs showing greater nicotine lever activity overall. Developmental temporalâlimbic abnormalities that produce mental illness can thus generate adult polydrug addiction vulnerability as a mechanism independent from putative crossâsensitization effects between addictive drugs. Further preclinical modeling of thirdâorder (and higher) addictionâmental illness comorbidities may advance our understanding and treatment of these complex, yet common brain illnesses
Targeting Glutamate Uptake To Treat Alcohol Use Disorders
Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence
Ethanol increases glutamate neurotransmission in the posterior ventral tegmental area of female Wistar rats
Backgroundâ
The posterior ventral tegmental area (pVTA) mediates the reinforcing and
stimulating effects of ethanol (EtOH). Electrophysiological studies indicated that exposure to
EtOH increased glutamate synaptic function in the VTA. The current study determined the
neurochemical effects of both acute and repeated EtOH exposure on glutamate neurotransmission
in the pVTA.
Methodsâ
Adult female Wistar rats were implanted with microdialysis probes in the pVTA.
During microdialysis, rats received acute i.p. injection of saline or EtOH (0.5, 1.0 or 2.0 g/kg) and
extracellular glutamate levels were measured in the pVTA. The effects of repeated daily injections
of EtOH (0.5, 1.0, or 2.0 g/kg) on basal extracellular glutamate concentrations in the pVTA and on
glutamate response to a subsequent EtOH challenge were also examined.
Resultsâ
The injection of 0.5 g/kg EtOH significantly increased (120â125 % of baseline),
whereas injection of 2.0 g/kg EtOH significantly decreased (80% of baseline) extracellular
glutamate levels in the pVTA. The dose of 1.0 g/kg EtOH did not alter extracellular glutamate
levels. Seven repeated daily injections of each dose of EtOH increased basal extracellular
glutamate concentrations (from 4.1 Âą 0.5 to 9.2 Âą 0.5 ÎźM) and reduced glutamate clearance in the
pVTA (from 30 Âą 2% to 17 Âą 2%), but failed to alter glutamate response to a 2.0 g/kg EtOH
challenge.
Conclusionâ
The results suggest that the low dose of EtOH can stimulate the release of
glutamate in the pVTA, and repeated EtOH administration increased basal glutamate transmission
in the pVTA, as a result of reduced glutamate clearance
Caffeinated Alcoholic Beverages â An Emerging Trend in Alcohol Abuse
Alcohol use disorders are pervasive in society and their impact affects quality of life, morbidity and mortality, as well as individual productivity. Alcohol has detrimental effects on an individualâs physiology and nervous system, and is associated with disorders of many organ and endocrine systems impacting an individualâs health, behavior, and ability to interact with others. Youth are particularly affected. Unfortunately, adolescent usage also increases the probability for a progression to dependence. Several areas of research indicate that the deleterious effects of alcohol abuse may be exacerbated by mixing caffeine with alcohol. Some behavioral evidence suggests that caffeine increases alcohol drinking and binge drinking episodes, which in turn can foster the development of alcohol dependence. As a relatively new public health concern, the epidemiological focus has been to establish a need for investigating the effects of caffeinated alcohol. While the trend of co-consuming these substances is growing, knowledge of the central mechanisms associated with caffeinated ethanol has been lacking. Research suggests that caffeine and ethanol can have additive or synergistic pharmacological actions and neuroadaptations, with the adenosine and dopamine systems in particular implicated. However, the limited literature on the central effects of caffeinated ethanol provides an impetus to increase our knowledge of the neuroadaptive effects of this combination and their impact on cognition and behavior. Research from our laboratories indicates that an established rodent animal model of alcoholism can be extended to investigate the acute and chronic effects of caffeinated ethanol
Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders
Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs
The Reinforcing Properties of Drugs of Abuse are Attenuated by Naltrexone in Caenorhabditis elegans
poster abstractDrug addiction is a chronic, relapsing disease premised on compulsive drug seeking.
Previous work from our lab demonstrated that the nematode Caenorhabditis elegans
(C. elegans) can be used to examine the reinforcing properties of drugs of abuse. A
successful model for studying the reinforcing effects of drugs in C. elegans would
greatly aid efforts to discover potential therapeutic interventions for drug addiction.
The present study examined preference for morphine, ethanol, cocaine, and a
cannabinoid agonist (CB agonist) in C. elegans and the effect of naltrexone, an opioid
antagonist, on this behavior. Six-well agar test plates were utilized to test drug
preference. Each well had two circular target zones equidistant from the center; 4Îźl
of the targeted drug or water were placed in the center of one of the two target zones
within each well. Worms in one group were pre-treated with 10mM naltrexone, while
controls were pre-treated with 0.97 mM HCl for 30 min prior to testing. Worms in
each treatment group were then placed in the center of each well and allowed to move
freely for 30 minutes-images were captured at 10 and 30 minutes. Animals treated
with vehicle displayed a significant preference for the aforementioned drugs relative
to controls; naltrexone pretreatment significantly ameliorated this effect. Naltrexone
had no effect on food or chemoatractant preference, indicating that the effects of
naltrexone on drug preference are selective and not due to disruption in general
behaviors. These findings suggest that the reinforcing properties of drugs of abuse
can be examined in C. elegans and this model may be useful for screening potential
pharmacotherapies for drug abuse
Microinjections of acetaldehyde or salsolinol into the posterior ventral tegmental area increase dopamine release in the nucleus accumbens shell
BACKGROUND: Published findings indicate that acetaldehyde (ACD; the first metabolite of ethanol [EtOH]) and salsolinol (SAL; formed through the nonenzymatic condensation of ACD and dopamine [DA]) can be formed following EtOH consumption. Both ACD and SAL exhibit reinforcing properties within the posterior ventral tegmental area (pVTA) and both exhibit an inverted "U-shaped" dose-response curve. The current study was undertaken to examine the dose-response effects of microinjections of ACD or SAL into the pVTA on DA efflux in the nucleus accumbens shell (AcbSh).
METHODS: For the first experiment, separate groups of male Wistar rats received pulse microinjections of artificial cerebrospinal fluid (aCSF) or 12-, 23-, or 90-ÎźM ACD into the pVTA, while extracellular DA levels were concurrently measured in the AcbSh. The second experiment was similarly conducted, except rats were given microinjections of aCSF or 0.03-, 0.3-, 1.0-, or 3.0-ÎźM SAL, while extracellular levels of DA were measured in the AcbSh.
RESULTS: Both ACD and SAL produced a dose-dependent inverted "U-shaped" response on DA release in the AcbSh, with 23-ÎźM ACD (200% baseline) and 0.3-ÎźM SAL (300% baseline) producing maximal peak responses with higher concentrations of ACD (90 ÎźM) and SAL (3.0 ÎźM) producing significantly lower DA efflux.
CONCLUSIONS: The findings from the current study indicate that local application of intermediate concentrations of ACD and SAL stimulated DA neurons in the pVTA, whereas higher concentrations may be having secondary effects within the pVTA that inhibit DA neuronal activity. The present results parallel the studies on the reinforcing effects of ACD and SAL in the pVTA and support the idea that the reinforcing effects of ACD and SAL within the pVTA are mediated by activating DA neurons
Scheduled access alcohol drinking by alcohol-preferring (P) and high-alcohol-drinking (HAD) rats: modeling adolescent and adult binge-like drinking
Binge alcohol drinking continues to be a public health concern among todayâs youth and young adults. Moreover, an early onset of alcohol use, which usually takes the form of binge drinking, is associated with a greater risk for developing alcohol use disorders. Given this, it is important to examine this behavior in rat models of alcohol abuse and dependence. Toward that end, the objective of this article is to review findings on binge-like drinking by selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of rats. As reviewed elsewhere in this special issue, the P line meets all, and the HAD line meets most, of the proposed criteria for an animal model of alcoholism. One model of binge drinking is scheduled ethanol access during the dark cycle, which has been used by our laboratory for over 20 years. Our laboratory has also adopted a protocol involving the concurrent presentation of multiple ethanol concentrations. When this protocol is combined with limited access, ethanol intake is maximized yielding blood ethanol levels (BELs) in excess, sometimes greatly in excess, of 80 mg%. By extending these procedures to include multiple scheduled ethanol access sessions during the dark cycle for 5 consecutive days/week, P and HAD rats consume in 3 or 4 h as much as, if not more than, the amount usually consumed in a 24-h period. Under certain conditions, using the multiple scheduled access procedure, BELs exceeding 200 mg% can be achieved on a daily basis. An overview of findings from studies with other selectively bred, inbred, and outbred rats places these findings in the context of the existing literature. Overall, the findings support the use of P and HAD rats as animal models to study binge-like alcohol drinking and reveal that scheduled access procedures will significantly increase ethanol intake by other rat lines and strains as well
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