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- Bendre, Megha, et al.
(author)
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Early life stress and voluntary alcohol consumption in relation to Maoa methylation in male rats.
- 2019
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In: Alcohol. - : Elsevier BV. - 0741-8329 .- 1873-6823. ; 79, s. 7-16
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Journal article (peer-reviewed)abstract
- Early life stress (ELS) or alcohol consumption can influence DNA methylation and affect gene expression. The monoamine oxidase A (Maoa) encodes the enzyme that metabolizes monoaminergic neurotransmitters crucial for the stress response, alcohol reward, and reinforcement. Previously, we reported lower Maoa expression in the nucleus accumbens and dorsal striatum of male rats exposed to ELS during the first three postnatal weeks, and to voluntary alcohol consumption in adulthood, compared with controls. The present study continued to investigate the effect of ELS and alcohol consumption on Maoa methylation, and its relation to Maoa expression in these animals. We selected candidate CpGs after performing next-generation bisulfite sequencing of the Maoa promoter, intron 1-5, exons 5 and 6, together comprised of 107 CpGs, in a subgroup of rats. Pyrosequencing was used to analyse the methylation of ten candidate CpGs in the promoter and intron 1 in the entire sample. ELS and alcohol displayed an interaction effect on CpG-specific methylation in the dorsal striatum. CpG-specific methylation correlated with Maoa expression, corticosterone levels, and alcohol consumption in a brain region-specific manner. CpG-specific methylation in the Maoa promoter was a potential moderator of the interaction of ELS with alcohol consumption on Maoa expression in the NAc. However, the findings were sparse, did not survive correction for multiple testing, and the magnitude of differences in methylation levels was small. In conclusion, CpG-specific Maoa methylation in the promoter and intron 1 may associate with ELS, alcohol consumption and Maoa expression in reward-related brain regions.
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- Ciccocioppo, Roberto, et al.
(author)
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Stress-related neuropeptides and alcoholism : CRH, NPY, and beyond
- 2009
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In: Alcohol. - : Elsevier. - 0741-8329 .- 1873-6823. ; 43:7, s. 491-498
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Journal article (peer-reviewed)abstract
- This article summarizes the proceedings of a symposium held at the conference on "Alcoholism and Stress: A Framework for Future Treatment Strategies" in Volterra, Italy, May 6-9, 2008. Chaired by Markus Heilig and Roberto Ciccocioppo, this symposium offered a forum for the presentation of recent data linking neuropetidergic neurotransmission to the regulation of different alcohol-related behaviors in animals and in humans. Dr. Donald Gehlert described the development of a new corticotrophin-releasing factor receptor 1 antagonist and showed its efficacy in reducing alcohol consumption and stress-induced relapse in different animal models of alcohol abuse. Dr. Andrey Ryabinin reviewed recent findings in his laboratory, indicating a role of the urocortin 1 receptor system in the regulation of alcohol intake. Dr. Annika Thorsell showed data supporting the significance of the neuropeptide Y receptor system in the modulation of behaviors associated with a history of ethanol intoxication. Dr. Roberto Ciccocioppo focused his presentation on the nociceptin/orphanin FQ (N/OFQ) receptors as treatment targets for alcoholism. Finally, Dr. Markus Heilig showed recent preclinical and clinical evidence suggesting that neurokinin 1 antagonism may represent a promising new treatment for alcoholism. Collectively, these investigators highlighted the significance of neuropeptidergic neurotransmission in the regulation of neurobiological mechanisms of alcohol addiction. Data also revealed the importance of these systems as treatment targets for the development of new medication for alcoholism.
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- Cippitelli, Andrea, et al.
(author)
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The novel, selective, brain-penetrant neuropeptide Y Y2 receptor antagonist, JNJ-31020028, tested in animal models of alcohol consumption, relapse, and anxiety
- 2011
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In: Alcohol. - : Elsevier. - 0741-8329 .- 1873-6823. ; 45:6, s. 567-576
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Journal article (peer-reviewed)abstract
- Neuropeptide Y (NPY) signaling has been shown to modulate stress responses and to be involved in regulation of alcohol intake and dependence. The present study explores the possibility that blockade of NPY Y2 autoreceptors using a novel, blood-brain barrier penetrant NPY Y2 receptor antagonist, JNJ-31020028 (N-(4-{4-[2-(diethylamino)-2-oxo-1-phenylethyl]piperazin-1-yl}-3-fluorophenyl)-2-pyridin-3-ylbenzamide), may achieve a therapeutically useful activation of the NPY system in alcohol- and anxiety-related behavioral models. We examined JNJ-31020028 in operant alcohol self-administration, stress-induced reinstatement to alcohol seeking, and acute alcohol withdrawal (hangover)-induced anxiety. Furthermore, we tested its effects on voluntary alcohol consumption in a genetic animal model of alcohol preference, the alcohol-preferring (P) rat. Neither systemic (0, 15, 30, and 40 mg/kg, subcutaneously [s.c.]) nor intracerebroventricular (0.0, 0.3, and 1.0 nmol/rat) administration of JNJ-31020028 affected alcohol-reinforced lever pressing or relapse to alcohol seeking behavior following stress exposure. Also, when its effects were tested on unlimited access to alcohol in P rats, preference for alcohol solution was transiently suppressed but without affecting voluntary alcohol intake. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of NPY Y2 antagonism. Our data do not support Y2 antagonism as a mechanism for reducing alcohol consumption or relapse-like behavior, but the observed effects on withdrawal-induced anxiety suggest that NPY Y2 receptor antagonists may be a putative treatment for the negative affective states following alcohol withdrawal.
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- Hunsberger, Monica, 1973, et al.
(author)
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Regular versus episodic drinking in Swedish women: Reporting of regular drinking may be less biased by social desirability.
- 2020
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In: Alcohol. - : Elsevier BV. - 1873-6823 .- 0741-8329. ; 86, s. 57-63
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Journal article (peer-reviewed)abstract
- To describe the personality and social characteristics associated with regular and episodic alcohol consumption in a Swedish cohort of women.406 women aged 38 and 50 who participated in the Population Study of Women in Gothenburg in 2004-2005 with complete data on the key variables are included. Regular alcohol use was based on frequencies of alcoholic beverage consumption, reported to examining physicians. Regular drinking was defined as those consuming wine, beer, or spirits at least twice weekly. Episodic drinking was defined as consumption of six drinks or more on a single occasion at least once during the last year. Personality traits were studied using the self-administered 57-item Eysenck Personality Inventory, which includes a 'lie scale' measuring the tendency toward social desirability, a 'neuroticism scale', and an 'extraversion scale'. Logistic regression was used to estimate odds ratios (OR) for regular and episodic drinking, respectively, in relation to standardized (SD) personality scores and selected social characteristics.49% of the women reported episodic drinking, while 58% reported regular drinking, and 34% reported both. Women with a higher tendency toward socially desirable responses were less likely to report episodic drinking (odds ratio [OR]=0.67, 95% confidence interval [CI]=0.53-0.84) per standard deviation (SD), a trait that was not associated with regular drinking.The strong inverse association between the propensity to lie scale with episodic but not regular drinking suggests that episodic drinking is subject to greater social desirability and under-reporting biases than regular drinking. Our findings indicate that this type of problem drinking may be missed in medical examinations, which limits the ability of health professionals to intervene.
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- Jerlhag, Elisabeth, 1978, et al.
(author)
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The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice.
- 2011
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In: Alcohol. - : Elsevier BV. - 1873-6823 .- 0741-8329. ; 45:4, s. 341-347
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Journal article (peer-reviewed)abstract
- Ghrelin, the first endogenous ligand for the type 1A growth hormone secretagogue receptor (GHS-R1A), plays a role in energy balance, feeding behavior, and reward. Previously, we showed that pharmacologic and genetic suppression of the GHS-R1A attenuates the alcohol-induced stimulation, accumbal dopamine release, and conditioned place preference as well as alcohol consumption in mice, implying that the GHS-R1A is required for alcohol reward. The present study further elucidates the role of ghrelin for alcohol-induced dopamine release in nucleus accumbens and locomotor stimulation by means of ghrelin knockout mice. We found that the ability of alcohol to increase accumbal dopamine release in wild-type mice is not observed in ghrelin knockout mice. Furthermore, alcohol induced a locomotor stimulation in the wild-type mice and ghrelin knockout mice; however, the locomotor stimulation in homozygote mice was significantly lower than in the wild-type mice. The present series of experiments suggest that endogenous ghrelin may be required for the ability of alcohol to activate the mesolimbic dopamine system.
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