| 1. |
- Fried, Ulrik, et al.
(författare)
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Chronic ethanol exposure enhances activating protein-1 transcriptional activity in human neuroblastoma cells
- 2001
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Ingår i: Alcohol. - 0741-8329. ; 24:3, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- This study demonstrates a method for studying the effects of ethanol on transcription mediated by activating protein-1 (AP-1). The effects of ethanol on AP-1 activity and on the signaling cascades in this process were investigated by using a reporter gene technique with secreted alkaline phosphatase as the reporter gene coupled to nine DNA AP-1-binding elements. Long-term ethanol exposure (48-72 h) dose dependently enhanced AP-1 transcriptional activity in SH-SY5Y cells. Shorter exposure periods with ethanol did not influence AP-1 transcriptional activity compared with findings for control cells. Inhibition of protein kinase C (PKC) dramatically decreased AP-1 activity in both control and ethanol-exposed cells and abolished the ethanol enhancement. This finding suggests a pivotal role for PKC-coupled signaling in AP-1 transcriptional activity. Phorbol ester stimulation of AP-1 transcriptional activity was not influenced by long-term ethanol exposure. This finding indicates that signaling events upstream of PKC are the targets for ethanol. Mitogen-activated protein kinases ERK and p38 may play a role in ethanol-enhanced AP-1 activity because inhibitors of both enzymes partly reduced the enhancement. The inhibitors also partly blocked phorbol ester-induced AP-1 activation, which demonstrates a function of these mitogen-activated protein kinases downstream of PKC.
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| 2. |
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| 3. |
- Berggren, Ulf, et al.
(författare)
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Extremely long recovery time for the sedative effect of clonidine in male type 1 alcohol-dependent subjects in full sustained remission
- 2002
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Ingår i: Alcohol. - 0741-8329. ; 28, s. 181-187
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Tidskriftsartikel (refereegranskat)abstract
- The possible relation between alpha-2-adrenoceptor function - as assessed by changes in systolic and diastolic blood pressure and heart rate, as well as level of sedation, after administration of clonidine (2.0 μg/kg, i.v.) - and length of time of alcohol dependence or duration of remission was investigated in 17 male subjects with alcohol dependence in full sustained remission. Six healthy males were used as control subjects. The clonidine-induced scores for level of sedation were found to correlate with duration of time in remission (r = 0.60; P < .02). Median split of duration of remission revealed that subjects with short-term (2 ± 1 years) duration of remission had significantly lower scores for clonidine-induced level of sedation than the scores for both subjects with long-term (12 ± 5 years) duration of remission (P < .004) and control subjects (P < .02). There was also a significant correlation between duration of remission and values for clonidine-induced reduction of systolic blood pressure (r = 0.51; P < .05). Results indicate an extremely long recovery period in some aspects of alpha-2-adrenoceptor function, especially for clonidine-induced increase in level of sedation, with a normalization time of 4 to 5 years. © 2002 Elsevier Science Inc. All rights reserved.
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| 4. |
- Eriksson, Matts, 1960, et al.
(författare)
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Further investigation of citalopram on alcohol consumption in heavy drinkers: Responsiveness possibly linked to the DRD2 A2/A2 genotype
- 2001
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Ingår i: Alcohol. - 0741-8329. ; 24, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- Citalopram, a selective serotonin reuptake inhibitor, has been suggested to reduce alcohol intake, at least in some studies. The present study aimed to replicate our earlier finding that citalopram reduces alcohol intake only in subjects with a weekly consumption ranging between 300 and 800 g of pure alcohol. Subjects (n=37) in this study were therefore randomized into a double-blind treatment with either 40 mg of citalopram daily or placebo for a 4-week period. Another purpose was to investigate whether different measures of central neurotransmission might predict an effect of citalopram or placebo on alcohol consumption. Therefore, prolactin response to d-fenfluramine, platelet monoamine oxidase-B activity, as well as the genotype of the dopamine D2 receptor (DRD2), A1 and A2 alleles, were determined and related to individual changes in alcohol consumption. Citalopram was not found to be superior to placebo in reducing alcohol intake. Prolactin responses to d-fenfluramine and levels of platelet monoamine oxidase-B activities were not related to changes in alcohol consumption, regardless of treatment with citalopram or placebo. When subjects were grouped according to the presence or absence of the DRD2 A1 allele, those with the genotype DRD2 A2/A2 were found to transiently reduce their alcohol consumption during citalopram treatment. This finding seems to indicate that, in subjects with heavy alcohol consumption, possession of the genotype DRD2 A2/A2 may be prerequisite for a treatment effect of citalopram. Copyright © 2001 Elsevier Science Inc.
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| 5. |
- Eriksson, Matts, et al.
(författare)
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Mental well-being in subjects with long-term excessive alcohol consumption: An experimental study
- 2002
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Ingår i: Alcohol. - 0741-8329. ; 27, s. 99-105
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Tidskriftsartikel (refereegranskat)abstract
- Daily self-reports on six dimensions of mental well-being, with the use of the Swedish Mood Adjective Check List (sMACL), were investigated in 61 socially stable and physically and mentally healthy subjects with long-term excessive alcohol consumption (113 ± 42 g of pure alcohol daily) during a 7-week study. At the start of the study, all subjects had low levels of mental well-being compared with those for a norm group, most markedly among those who did not complete the study period (n = 20). At the end of the investigation, subjects who completed the study (n = 41) had levels of mental well-being similar to those of a norm group. Subjects who reduced their alcohol consumption by 60% did not differ in levels of mental well-being compared with subjects without reduction in intake. No differences in levels of mental well-being were observed in subjects treated with citalopram compared with those given placebo. © 2002 Elsevier Science Inc. All rights reserved.
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| 6. |
- Eriksson, Matts, et al.
(författare)
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No effect of the cortisol-synthesis inhibitor metyrapone on alcohol drinking: A pilot study
- 2001
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Ingår i: Alcohol. - 0741-8329. ; 25, s. 115-122
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Tidskriftsartikel (refereegranskat)abstract
- Two bases for this study were the theory of stress as a provoking factor for high alcohol consumption in human being and findings that the stress hormones stimulate ethanol intake in rats. We therefore investigated whether the cortisol-synthesis inhibitor metyrapone could reduce high alcohol consumption in socially stable subjects who reported drinking mainly for relaxation purposes. Most of the investigated subjects were found to be alcohol dependent (81%), with moderately high levels of intake, yet they had not reported more severe life problems. All subjects reported their daily alcohol consumption during 2-week baseline, medication, and postmedication periods. Sixteen subjects were given 1 g of metyrapone orally daily for 14 days, and 15 subjects received placebo. Morning serum cortisol concentration was assessed four times in the course of the study period. Metyrapone treatment was not found to reduce alcohol consumption more than placebo. Serum cortisol concentrations remained within the laboratory reference interval during the study and did not differ between the study groups. In this study, we found that a cortisol-synthesis inhibitor had no effect on alcohol consumption. One reason may be that cortisol secretion has no role in the maintenance of high alcohol consumption. On the other hand, because this study is the first of its kind, further studies with the use of other doses of treatment and treatment schedules are suggested. © 2001 Elsevier Science Inc. All rights reserved.
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| 9. |
- Lindholm, Sara, et al.
(författare)
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Repeated ethanol administration induces short- and long-term changes in enkephalin and dynorphin tissue concentrations in rat brain
- 2000
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Ingår i: Alcohol. - 0741-8329 .- 1873-6823. ; 22:3, s. 165-171
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we have shown that rats repeatedly treated with ethanol and/or cocaine have decreased kappa-opioid receptor mRNA levels in the mesolimbic system. The aim of the present study was to investigate the short- and long-term effects of repeated ethanol administration on opioid peptide concentrations in brain tissue of male Sprague-Dawley rats. Dynorphin B (1-13) (Dyn B) and Met-enkephalinArg(6)Phe(7) (MEAP), endogenous ligands to kappa- and delta-opioid receptors, respectively, were measured using radioimmunoassays. The rats were given either ethanol [intraperitoneal (ip), twice daily, 2 g/kg bw/dose] or saline for 13 consecutive days. Thirty minutes after the last ethanol dose on Day 13, the Dyn B tissue concentration was significantly decreased in the cingulate cortex. The MEAP tissue concentration was decreased in the hippocampus 5 days after the last ethanol injection as compared to saline-treated controls. Furthermore, the Dyn B and the MEAP concentrations were increased in the periaqueductal grey area (PAG) at this time point. Of particular interest were the significant increases in Dyn B tissue concentrations found in the nucleus accumbens (NAcc) at 30 min and at 21 days after the last ethanol dose. The results suggest that repeated ethanol administration induces both short- and long-term changes in the tissue concentrations of opioids in certain brain regions associated with motivation and reward.
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