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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 611 (1990), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  Maternal alcohol consumption is a major health hazard for the fetus. Sweden has an extensive system of public antenatal care clinics, whose mission is to detect and prevent this type of health hazards. However, very few cases of alcohol consumption during pregnancy are detected. The aim of this study was to examine the prevalence of hazardous or harmful alcohol consumption during pregnancy in a consecutive series of Swedish pregnant females.Design, setting, participants and measurements  The Alcohol Use Disorders Identification Test (AUDIT) was used to collect anonymous data from consecutive pregnant subjects admitted during 1 year to an antenatal clinic in Stockholm, and signing up for parental education offered routinely (n = 1327). Data were obtained from 1101 subjects, typically in pregnancy week 30. A complete AUDIT form was filled out referring to alcohol use during the year prior to pregnancy. A separate form with the consumption items from AUDIT was filled out to report behaviour during pregnancy.Findings  For the year preceding pregnancy, 17% of subjects reported AUDIT scores of 6 or higher, indicating hazardous or harmful alcohol use in women. Few individuals reported scores of 13 or higher (indicating abuse or dependence), but almost half the subjects (46%) reported binge drinking (six standard drinks on a single occasion) once/month or more often, and 6% reported binge drinking on every occasion of alcohol consumption. One-third of the subjects (30%) continued regular alcohol use during pregnancy, and 6% reported consumption two to four times/month. In a logistic regression model, AUDIT scores for the year prior to pregnancy and subject age, but not education level were significant predictors of continued alcohol use during pregnancy.Conclusions  Alcohol use during pregnancy is more extensive than has been presumed in Sweden. Simple, clinically useful screening methodology detects hazardous consumption during pregnancy in a manner which regular antenatal care does not. If this methodology can be shown to have similar sensitivity when administered under non-anonymous conditions, it should be made part of routine antenatal care.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Addiction 100 (2005), S. 0 
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  To illustrate how modern neurobiological approaches will help to identify the neurocircuits and genes involved in addictive behavior.Background  The current disorder concept of addiction includes neurobiological foundations and neurobiological research assuming irreversible molecular and structural changes within the brain dopamine reinforcement system, constituting the ‘molecular and structural switch’ from controlled drug intake to compulsive drug abuse. However, those irreversible changes have not so far been identified and it is suggested that in addition to the mesolimbic dopamine system, other brain systems including the mesocortical and nigrostriatal pathways as well as their non-dopaminergic feedback-loops might be involved in addictive behavior.Neurobiological approach  A three-step neurobiological approach is described that allows in a first step via novel animal models and imaging techniques to identify the neuroanatomical sites mediating voluntary drug intake, reinstatement of drug-seeking behavior, relapse, loss of control and drug intake despite negative consequences. In a subsequent step, forward genetic approaches including quantitative trait loci (QTL)-analysis and gene expression profiling are helpful in identifying so-called candidate genes. In a final step, conditional animal mutants and selective pharmacological tools are used to functionally validate candidate genes. Following this validation process, the transfer to the human situation has to be made and candidate genes have to be verified further in well-phenotyped cohorts of addicted patients.Conclusion  This three-step neurobiological approach, that must involve an interdisciplinary team including experimental psychologists, geneticists, molecular biologists and finally clinical addiction researchers, will allow us to understand where and how the addicted brain goes awry.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Striatal c-fos induction was blocked by local administration of phosphorothioated c-fos antisense oligonucleotides (AS-ODN) to examine the possible role of caffeine-induced c-fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c-fos mRNA and Fos-protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c-fos AS-ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS-ODN was sequence specific. The antisense blockade of c-fos reduced the effect of caffeine on the expression of mRNAs for preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate–putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vivo studies of drug actions.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The endocannabinoid system is involved in a variety of effects of drugs of misuse, and blockade of the cannabinoid CB1 receptor by selective antagonists elicits marked reductions in opioid and alcohol self-administration. The present study was designed to extend our knowledge of the role of the cannabinoid CB1 receptor in the modulation of alcohol misuse vulnerability in rats. Accordingly, using nonselected Wistar rats and genetically selected Marchigian Sardinian alcohol-preferring (msP) rats, we investigated the effect of the CB1 antagonist SR141716A on operant alcohol self-administration and on reinstatement of alcohol-seeking behavior by environmental conditioning factors. In addition, in situ hybridization studies in both strains were performed to measure cannabinoid CB1 receptor mRNA in different brain areas of these animals. Results showed that intraperitoneal administration of SR141716A (0.03, 1.0 and 3.0 mg/kg) markedly inhibits ethanol self-administration and conditioned reinstatement of ethanol-seeking behavior in both strains of rats. ED50 analysis showed significantly higher sensitivity (P 〈 0.05) to the effect of SR141716A in msP rats than in heterogeneous Wistar rats. In situ hybridization studies revealed that, compared with Wistar rats, msP animals have consistently greater cannabinoid CB1 receptor mRNA expression in a number of brain areas, including the frontoparietal cortex, caudate-putamen and hippocampus (CA1 and dentate gyrus areas). In conclusion, we provide clear evidence that blockade of CB1 receptors reduces both ethanol self-administration and conditioned reinstatement of alcohol-seeking behavior in rats. In addition, current pharmacological and neuroanatomical data suggest that an altered function of the CB1 receptor system exists between genetically selected alcohol-preferring msP rats and a heterogeneous animal population.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Neuropeptide Y ; Anxiolysis ; Conflict model ; Alpha-adrenergic ; Idazoxan ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of intracerebroventircular (ICV), neuropeptide Y (NPY) (0.2–5.0 nmol) and its C-terminal 13–36 amino acid (AA) fragment (0.4–2.0 nmol) have been examined with respect to anxiolytic properties in two rat anxiety models, Montgomery's conflict test (MT), and Vogel's drinking conflict test (VT). In the MT, 1.0 and 5.0 nmol NPY abolished the normal preference for the closed arms of the maze. At 5.0 nmol, the total number of entries made into both closed and open arms was decreased by 50%. In the VT, both 0.2 and 1.0 nmol NPY markedly increased the number of shocks accepted. The effect of 5.0 nmol NPY was less pronounced. In control experiments, NPY (0.2 nmol) did not affect pain sensitivity or thirst. Pretreatment with the selective alpha2-adrenergic receptor antagonist idazoxan, at a dose which by itself did not affect behaviour (2.0 mg/kg), antagonized the effect of 1.0 nmol NPY in the VT. NPY 13-36 was without significant effect in both models. The results suggest that NPY exerts anxiolytic-like effects, and that these effects are mediated through an interaction with noradrenergic systems. Higher doses of NPY produce sedation and ataxia, which decrease overall activity in the MT, and interfere with the ability fully to express behaviourally the anxiolytic-like effect in the VT. The findings are discussed in relation to the noradrenaline hypothesis of anxiety, and to observations indicating involvement of NPY in the pathophysiology of major depression.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1912
    Keywords: Key words Antisense ; Dopamine ; Dopamine D3 ; receptor ; Radioligand binding ; In vivo microdialysis ; Behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A 15-mer, all-phosphorothioate-modified antisense oligodeoxynucleotide (ASO) targeted against rat dopamine D3 receptor mRNA (4 µM, 5 days) significantly reduced (28%) the amount of binding sites labelled with [3H]spiperone in monolayer cultured Chinese hamster ovary (CHO) cells transfected with the complementary desoxyribonucleic acid (cDNA) for the rat D3 receptor. In contrast, D3-ASO treatment did not reduce the amount of bound [3H]spiperone in CHO cells transfected with D2 receptor cDNA. Intracerebroventricular infusion of D3-ASO (osmotic minipump, 10 µg/µl/h, 7 days) influenced dopamine receptor density in the limbic forebrain such that the upper part of the dopamine/[3H]spiperone displacement curve – tentatively representing the D3 receptor – was altered significantly. Spontaneous locomotor activity of non-habituated rats was increased significantly in D3-ASO-treated animals; in addition, in vivo microdialysis revealed a moderate increase in dopamine release in the nucleus accumbens in these animals. In all experiments, an oligodeoxynucleotide comprising the same nucleotides as the antisense sequence, but in random order, was used as control. It is concluded that the antisense strategy is useful for investigating the functional role of dopamine D3 receptors and that the dopamine D3 receptor is involved in rat locomotor behaviour.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular neurobiology 14 (1994), S. 415-423 
    ISSN: 1573-6830
    Keywords: c-fos ; amygdala ; antisense ; Vogel conflict test ; fear ; anxiety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. The amygdaloid complex is a key structure in mechanisms of fear and anxiety. Expression of the immediate-early gene c-fos has been reported in the central nucleus of the amygdala following various stressors, but the functional role of this phenomenon has remained unknown. 2. c-fos expression was observed in the central nucleus when rats were subjected to a pharmacologically validated animal model of anxiety, the Vogel conflict test, but not after mere exposure to the test apparatus. Bilateral amygdala injection of a 15-mer phosphorothioate c-fos antisense oligodeoxynucleotide prior to testing blocked conflict-induced c-fos expression and had behavioral effects similar to those of established antianxiety drugs. 3. Separate experiments determined that antisense treatment did not affect conflict behavior by acting on shock thresholds or drinking motivation. 4. These findings provide evidence that neuronal activation and c-fos induction in the amygdala may be of importance for mechanisms of fear and anxiety.
    Type of Medium: Electronic Resource
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