bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage for Platelet Monoamine Oxidase (MAO) Activity: Results from a Replication Sample
Authors: Saccone Nancy L. , Rice John P. , Rochberg Nan , Williams Jeff T. , Goate Alison , Reich Theodore , Edenberg Howard J. , Foroud Tatiana , Nurnberger John I. , Bierut Laura J. , Crowe Raymond , Li Ting‐Kai 
Published: April 2006

Background: Monoamine oxidase B (MAO‐B) degrades catecholamines in presynaptic nerve endings and is also active in platelets. There is evidence to suggest that platelet MAO‐B activity level is controlled by a major genetic locus distinct from the structural gene on the X chromosome. To expand on a prior report, new linkage analyses for platelet MAO‐B activity have been performed on the previously analyzed sample (designated the initial sample), on a new sample of families (the replication sample), and on the combined sample. These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA).Methods: The initial sample consists of 105 extended families providing 1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO activity and genotyped. The replication sample of 157 extended families contains 608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses were conducted using Haseman‐Elston based regression on sib pairs and variance component analysis on extended pedigrees, and the importance of cigarette smoking and gender as covariates of platelet MAO‐B activity was taken into account.Results: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for linkage across the two distinct datasets by at least one analysis method. Under Haseman‐Elston regression of independent sib pairs, only the chromosome 2 region gave lod scores above 1 in both the initial and replication samples. Using all possible pairs, unweighted, for the regression, chromosome 12 gave lod scores above 1 in both samples. For variance component analysis, only the chromosome 9 region gave lod scores above 1 in both samples.Conclusions: The consistency across datasets of these findings is encouraging. In particular, variance component analysis of extended pedigrees supports a potential linkage of MAO‐B activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined sample. Sib‐pair regression supports this finding with modest lod scores in the region. Suggestive linkage to chromosomes 2 and 12 from sib‐pair analysis is only weakly supported by variance component analysis.
Videotaped Cue for Urge to Drink Alcohol
Authors: Streeter Chris C. , Gulliver Suzy B. , Baker Errol , Blank Steven R. , Meyer Angela A. , Ciraulo Domenic A. , Renshaw Perry F. 
Published: April 2006

Background: The urge to drink alcohol can be robustly and reliably induced via actual exposure to a person's preferred alcoholic beverage. Unfortunately, these exposure paradigms are unwieldy for functional magnetic resonance imaging studies. The goal of this study was to examine whether viewing a personalized videotaped cue could induce alcohol craving. The following hypotheses were tested: (1) individualized cue videotapes can reliably elicit the urge to drink alcohol in alcohol‐dependent participants and (2) alcohol drinking histories can predict reactivity to cue.Methods: DSM‐IV criteria were used to identify an alcohol‐dependent group (ADG). Controls included a light‐drinking group and a moderate‐drinking group. Urge to drink alcohol was assessed at baseline and after each of five in vivo exposure conditions: water (W), alcohol 1 (A1), mood induction (M), alcohol 2 (A2), and relaxation (R). The entire exposure session was videotaped. Each participant's video footage was digitally edited to produce a 17.5‐min cue that was presented to the participant 24 to 72 hr later. Ratings of urge to drink alcohol across the five exposure conditions were compared for both the in vivo and the video exposure sessions.Results: Fourteen participants (five in the light‐drinking group, four in the moderate‐drinking group, and five in the ADG) completed both sessions. Participants in each group showed differences between neutral cue exposure (W and R) and alcohol‐related cue exposure (A1, M, and A2) in both the in vivo cue session (p < 0.002) and the videotape session (p < 0.02). Post hoc comparisons among the groups to alcohol‐related cues established that, in both sessions (pin vivo= 0.04;pvideotape= 0.04), the ADG demonstrated the greatest urge to drink.Conclusions: Alcohol cue reactivity can be reliably induced and assessed in alcohol‐dependent participants via personalized videotapes. History of alcohol consumption is positively correlated with the degree of cue reactivity. This study advances our ability to assess alcohol cue reactivity in the absence of alcohol.
Early Responsiveness to Stimuli Paired With Different Stages Within the State of Alcohol Intoxication
Authors: Pautassi Ricardo M. , Godoy Juan Carlos , Spear Norman E. , Molina Juan Carlos 
Published: April 2006

Background: Infant rats quickly learn to avoid a sensory cue paired with alcohol as an unconditioned stimulus, particularly when the drug reaches peak blood concentrations. In this study, a tactile cue paired with the onset of alcohol intoxication preceded subsequent presentations of a gustatory conditioned stimulus (CS). The goal was to address the possibility of differential conditioning depending on when stimuli were introduced during the course of the toxic state.Methods: In experiment 1, rat pups received sequential presentations of a salient texture (sandpaper) and a gustatory cue (saccharin) while intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture location tests and saccharin intake assessments were then performed. A third modality of assessment was defined by a saccharin intake test while pups simultaneously experienced sandpaper. In experiment 2, alcohol‐mediated conditioning was followed by tests similar to those of experiment 1, but after pups were re‐exposed to either the tactile CS or the alcohol‐unconditioned stimulus.Results: Conditioned taste aversions, due to pairing saccharin and the later stage of alcohol intoxication, were reliably established in both experiments. Also in both experiments, this excitatory aversive response was dramatically inhibited when the association between the texture CS and the earlier stage of alcohol intoxication was activated. There were no indications of conditioned motor responses to the tactile CS that might compete with intake behavior of saccharin or distort measurement of an appetitive memory derived from pairing the texture and the earlier stage of intoxication.Conclusions: Rat pups’ expression of an association between a taste signaling aversive consequences of alcohol was eliminated by the presence of a tactile stimulus that originally had signaled the absence of aversive consequences of alcohol intoxication. The results suggest the interaction of inhibitory and excitatory conditioning involving the aversive properties of alcohol.
Impairment of Neuronal Nitric Oxide Synthase‐Dependent Dilation of Cerebral Arterioles During Chronic Alcohol Consumption
Authors: Sun Hong , Patel Kaushik P. , Mayhan William G. 
Published: April 2006

Background: Although chronic alcohol consumption impairs endothelial nitric oxide synthase‐dependent reactivity of cerebral arterioles, the effect of alcohol consumption on vasodilation in response to activation of neuronal nitric oxide synthase (nNOS) has not been examined. Thus, our first goal was to determine whether chronic alcohol consumption impairs nNOS‐dependent reactivity of pial arterioles. Our second goal was to examine potential mechanisms for impaired responses of pial arterioles during chronic alcohol consumption.Methods: Sprague Dawley® rats were fed liquid diets with or without alcohol for 8 to 12 weeks. By using intravital microscopy, we measured the diameter of pial arterioles in response to nNOS‐dependent agonists—NMDA and kainate (KA)—in the absence and presence of NG‐monomethyl‐L‐arginine (L‐NMMA) or 7‐nitroindazole (7‐NI). We also measured responses of pial arterioles to nitroglycerin. Next, using Western blot analysis, we measured protein levels of the NMDA receptor subunit, KA receptor subunit, and nNOS protein in cerebral microvessels, parietal cortex, cerebellum, and brainstem of non‐alcohol‐fed and alcohol‐fed rats.Results: Topical application of NMDA (100 and 300 μM) and KA (100 and 300 μM) produced dose‐related dilation of pial arterioles in non‐alcohol‐fed and alcohol‐fed rats. However, the magnitude of vasodilation in response to NMDA and KA, but not nitroglycerin, was significantly less in alcohol‐fed compared with non‐alcohol‐fed rats. Topical application of L‐NMMA (10 μM) or 7‐NI (10 μM) significantly inhibited dilation of pial arterioles in response to NMDA and KA in non‐alcohol‐fed rats. In alcohol‐fed rats, only NMDA‐induced vasodilation was inhibited by L‐NMMA. In addition, we found that NMDA receptor subunit and KA receptor subunit protein levels increased in the parietal cortex and cerebellum of alcohol‐fed compared with non‐alcohol‐fed rats. However, no significant difference in protein level of nNOS was observed between non‐alcohol‐fed and alcohol‐fed rats.Conclusions: Our findings suggest that chronic alcohol consumption impairs nNOS‐dependent dilation of pial arterioles via a mechanism that appears to be unrelated to quantitative changes in NMDA receptors, KA receptors, or nNOS. Because the regulation of cerebral blood flow is influenced by neuronal activation, impaired reactivity of cerebral blood vessels to neuronal activation may contribute to the pathogenesis of cerebrovascular disorders observed during chronic alcohol consumption.
Hepatocyte Growth Factor, Epidermal Growth Factor, and Placenta Growth Factor Concentrations in Peripheral Blood of Pregnant Women With Alcohol Abuse
Authors: Vuorela Piia , Sarkola Taisto , Alfthan Henrik , Halmesmäki Erja 
Published: April 2006

Background: Alcohol abuse during pregnancy compromises fetal development not only directly but also by abnormal placental function. Therefore, hepatocyte growth factor (HGF), epidermal growth factor (EGF), and placenta growth factor (PlGF), expressed in the placenta, may play a role in alcohol‐induced placental dysfunction.Methods: Peripheral venous blood samples were collected from 40 pregnant alcohol‐abusing women and 42 abstinent pregnant women from gestational weeks 4 to 41. Plasma HGF and serum PlGF were assessed by enzyme‐linked immunosorbent assays and serum EGF by an immunofluorometric assay.Results: Plasma HGF concentrations were similar in alcohol‐abusing and abstinent mothers, although in the latter women these concentrations increased with advancing pregnancy. Serum EGF concentrations were consistently higher in alcohol‐abusing than in abstinent mothers. In the latter, these concentrations decreased with advancing pregnancy. Serum PlGF concentrations increased with advancing pregnancy in both groups and were higher in alcohol‐abusing mothers during the second and third trimesters but not during the first.Conclusions: Alcohol abuse during pregnancy is associated with changes in maternal circulating EGF and PlGF but not HGF concentrations. The observed changes may be caused by alcohol per se or may be secondary to possible alcohol‐induced changes in placental physiology.
Effect of Ethanol Self‐Administration on μ‐ and δ‐Opioid Receptor‐Mediated G‐Protein Activity
Authors: Sim‐Selley Laura J. , Sharpe Amanda L. , Vogt Leslie J. , Brunk Leah K. , Selley Dana E. , Samson Herman H. 
Published: April 2006

Background: This study examined the effects of ethanol self‐administration on μ‐ and δ‐opioid receptor‐mediated G‐protein activity in specific brain regions of male Long Evans rats.Methods: Rats were trained to self‐administer ethanol by using a home‐cage modification of the sucrose substitution paradigm. After 30 to 40 days of sucrose or sucrose/15% ethanol self‐administration (20 min sessions, Monday–Friday), rats were killed for autoradiographic assays. Coronal sections of brains from sucrose and ethanol self‐administering rats were collected and processed for basal and μ‐ and δ‐stimulated [35S]guanosine‐5′‐O‐(γ‐thio)‐triphosphate (GTPγS) binding. Sections were exposed to film and then analyzed by using computer‐assisted densitometry to determine levels of basal and agonist‐stimulated [35S]GTPγS binding.Results: μ‐Opioid‐stimulated [35S]GTPγS binding was decreased in the prefrontal cortex of brains from ethanol compared with sucrose self‐administering rats. μ‐Opioid‐stimulated [35S]GTPγS binding was unchanged in the cingulate cortex, caudate‐putamen, nucleus accumbens, amygdala, hypothalamus, thalamus, and locus ceruleus of ethanol compared with sucrose self‐administering rats. Basal and δ‐opioid‐stimulated [35S]GTPγS binding did not differ between the two groups in the prefrontal cortex or any other region analyzed.Conclusions: These data demonstrate decreased μ‐opioid‐mediated G‐protein activity in the prefrontal cortex of ethanol self‐administering rats and suggest an interaction between ethanol and μ‐opioid receptors in this region.
Sex Differences in Ethanol‐Induced Hypnosis and Hypothermia in Young Long‐Evans Rats
Authors: Webb Barbara , Burnett Patricia W. , Walker Don W. 
Published: April 2006

Introduction: Females experience greater liver damage, have reduced brain size, and have greater memory deficits than do males with a similar history of alcoholism. Females have higher peak alcohol levels and faster elimination rates than males. Our goal was to study sex differences in the response of young ethanol‐naïve outbred Long‐Evans rats to acute ethanol exposure so that we may better understand why females are more sensitive to alcohol toxicity than males.Methods: Females aged 49 days and males aged 43 days, weighing 153.6 and 177.5 g, respectively, were tested for their initial response to ethanol. Fasted (12 hr) females (in diestrous) and males were given an intraperitoneal injection of 3.0 g/kg of ethanol (v/v in 0.9% sterile saline). Body temperature, loss of the righting reflex (LORR), return of the righting reflex, and tail blood alcohol concentration (BAC) were monitored.Results: LORR occurred at the same time in females and males. The return of the righting reflex occurred later in males than in females. BACs were the same in the males and females except at LORR, when BAC was lower in the males. Acute ethanol tolerance developed in more males than females. Females demonstrated a slower recovery from peak ethanol‐induced hypothermia than males. The proportions of lean body mass, ethanol elimination, and ethanol metabolism were similar in the females and males.Conclusions: Ethanol‐naïve young male and female Long‐Evans rats demonstrated sex differences in their initial responses to ethanol. Males were more sensitive than females to the hypnotic effect of ethanol, whereas females were more sensitive than males to ethanol‐induced hypothermia. In addition, more males than females developed acute ethanol tolerance. Investigating the mechanisms underlying these differences may help us to understand why females experience more of the adverse effects of alcohol consumption than males.
Decreased Ethanol Preference and Consumption in Dopamine Transporter Female Knock‐Out Mice
Authors: Savelieva Katerina V. , Caudle W. Michael , Findlay Geoffrey S. , Caron Marc G. , Miller Gary W. 
Published: April 2006

Background: It is commonly believed that the mesolimbic dopamine (DA) system participates in the etiology of alcoholism. One of the most important regulators of DA synaptic transmission is the DA transporter (DAT). We examined the effects of the genetic reduction or deletion of DAT on voluntary ethanol consumption and ethanol‐induced sedation.Methods: Ethanol preference and consumption were assessed in the two‐bottle choice paradigm, and the depressant effects of ethanol were evaluated by measuring sleep time after acute injection of ethanol.Results: The latent period to lose the righting reflex was shorter in both knock‐out mice (DAT‐KO) and heterozygote mice (HET) than in wild‐type (WT) mice. No significant difference was found among the three genotypes in the ethanol blood concentration at the onset of regaining the righting reflex. Females of all genotypes consumed more fluid than males of the same genotype. HET and DAT‐KO females had increased total fluid consumption compared with WT females. DAT‐KO males had increased fluid consumption compared with WT and HET males. Ethanol preference and consumption were not different among male mice of different genotypes. WT and HET females demonstrated significantly higher ethanol consumption than males. HET female mice did not differ from WT mice in ethanol preference. There was no difference between HET and WT mice in the preference for saccharin or quinine solutions. DAT‐KO females avoided ethanol, and their consumption and preference were lower than in WT and HET females, despite markedly increased total intake. DAT‐KO mice also demonstrated altered taste preference for saccharin and quinine.Conclusions: Partial deletion of DAT results in increased fluid consumption in female mice but does not change ethanol preference in either sex. Complete deletion of DAT reduces ethanol preference in female mice; this may be due to a combination of the pharmacological actions of DAT deletion and alterations in fluid consumption and taste discrimination.
The Selectively Bred High Alcohol Sensitivity (HAS) and Low Alcohol Sensitivity (LAS) Rats Differ in Sensitivity to Nicotine
Authors: de Fiebre NancyEllen C. , Dawson Ralph , de Fiebre Christopher M. 
Published: April 2006

Background: Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated.Methods: Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine‐induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]α‐bungarotoxin in eight brain regions.Results: Both replicate HAS lines were more sensitive to nicotine‐induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine‐induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males.Conclusions: Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand‐binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.
Ethanol Sensitivity in ATP‐Gated P2X Receptors Is Subunit Dependent
Authors: Davies Daryl L. , Machu Tina K. , Guo Yumei , Alkana Ronald L. 
Published: April 2006

Background: P2X receptors are ligand‐gated cation channels that are gated by synaptically released extracellular adenosine 5′‐triphosphate (ATP). P2X receptors are inhibited by ethanol; however, few investigations have focused on ethanol's effects in P2X receptors. Recently, recombinant homomeric P2X4 receptors were reported to be sensitive to ethanol's inhibitory action, whereas recombinant P2X3 receptors were insensitive to ethanol. The two recombinant studies were conducted in different expression systems by using different techniques; therefore, questions remain. The present study tests the hypothesis that ethanol sensitivity in P2X receptors is subunit dependent.Methods: The effects of ethanol (25–200 mM ± ATP) on rat recombinant homomeric P2X2 and P2X4 receptors expressed in Xenopus oocytes were tested by using two‐electrode voltage clamp techniques.Results: Ethanol inhibited EC10 ATP‐gated currents significantly less in P2X2 versus P2X4 receptors. A second study found that ethanol right‐shifted the ATP concentration‐response curve in P2X2 receptors, which significantly increased the EC50 for ATP without altering the Hill slope or maximal current response to ATP. These latter characteristics of ethanol action in P2X2 receptors agree with previous work in P2X4 receptors. There was no effect of ethanol when tested in the absence of ATP.Conclusion: The findings are the first to show (1) ethanol inhibition of ATP‐activated currents on P2X2 receptors, (2) differences in ethanol sensitivity between homomeric P2X receptors when tested under matched conditions, and (3) evidence that suggests similar mechanisms of ethanol action for P2X2 and P2X4 receptors. These findings provide the first direct support for the hypothesis that ethanol sensitivity in P2X receptors is subunit dependent.
Alcohol Modulation of Neuronal Nicotinic Acetylcholine Receptors Is α Subunit Dependent
Authors: Zuo Yi , Kuryatov Alexander , Lindstrom Jon M. , Yeh Jay Z. , Narahashi Toshio 
Published: April 2006

Background: We have previously shown that n‐alcohols exert a dual action on the α4β2‐type neuronal nicotinic acetylcholine (ACh) receptors (AChRs), with shorter‐chain alcohols potentiating and longer‐chain alcohols inhibiting ACh‐induced currents. Ethanol potentiates the current in α4β2 receptors, yet it has little or no effect on the α3β2 receptors. Because the α4 AChRs are present predominantly in the brain, whereas the α3 AChRs are present predominantly in the peripheral ganglia, the differential action of ethanol on the α4β2 and α3β2 AChRs may contribute to its differential effects on the brain and the peripheral nervous system. The purpose of this study was to characterize the actions of alcohols on an α3‐containing nicotinic receptor and to further understand the mechanism underlying the differential action of ethanol on the two receptor subtypes.Methods: ACh‐induced currents were recorded from human α3β2 AChRs recombinantly expressed in human embryonic kidney tsA201 cells by using the whole‐cell patch clamp technique.Results: The ACh‐induced currents in the α3β2 receptors were potentiated by methanol and inhibited by longer‐chain alcohols. The transition point from potentiation to inhibition and the cutoff point were both shifted to shorter alcohols in the α3β2 AChR compared with the α4β2 AChR. This explains why ethanol, which was at the transition point, has little or no effect on the α3β2 AChR.Conclusions: The α3β2 AChRs are insensitive to ethanol because ethanol is at the transition point from potentiation to inhibition among n‐alcohols with different carbon‐chain lengths. The differential action on the α4β2 and α3β2 AChRs may explain the differential action of ethanol on the central nervous system.