bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethanol, Endocannabinoids, and the Cannabinoidergic Signaling System
Authors: Hungund Basalingappa L. , Basavarajappa Balapal S. , Vadasz Csaba , Kunos George , Rodriguez de Fonseca Fernando , Colombo Giancarlo , Serra Salvatore , Parsons Loren , Koob George F.
Published: April 2006

This article represents the proceedings of a symposium at the 2001 annual meeting of the Research Society on Alcoholism in Montreal, Canada. The chairpersons were Appa Hungund and George Koob. The presentations were (1) Role of endocannabinoids in ethanol tolerance, by Appa Hungund; (2) Modulation of cannabinoid receptor and its signal transduction in chronic alcoholism, by B. S. Basavarajappa; (3) Endocannabinoid involvement in the control of appetitive behavior, by George Kunos; (4) Regulation of voluntary ethanol intake by cannabinoid receptor agonists and antagonists in alcohol‐preferring sP rats, by Giancarlo Colombo; (5) Role of endogenous cannabinoid system in alcoholism, by Fernado Rodriguez de Fonseca; and (6) Endocannabinoids and dopamine interactions in vivo, by Loren Parsons and George Koob.
How Does Alcohol Contribute to Sexual Assault? Explanations from Laboratory and Survey Data
Authors: Abbey Antonia , Zawacki Tina , Buck Philip O. , Testa Maria , Parks Kathleen , Norris Jeanette , Martin Susan E. , Livingston Jennifer A. , McAuslan Pam , Monique Clinton A. , Kennedy Cheryl L. , George William H. , Cue Davis Kelly , Martell Joel
Published: April 2006

This article summarizes the proceedings of a symposium of the 2001 RSA Meeting in Montreal, Canada. The chair was Antonia Abbey and the organizers were Tina Zawacki and Philip O. Buck. There were four presentations and a discussant. The first presentation was made by Maria Testa whose interviews with sexual assault victims suggest that there may be differences in the characteristics of sexual assaults in which both the victim and perpetrator were using substances as compared to when only the perpetrator was using substances. The second presentation was made by Tina Zawacki whose research found that perpetrators of sexual assaults that involved alcohol were in most ways similar to perpetrators of sexual assaults that did not involve alcohol, although they differed on impulsivity and several alcohol measures. The third presentation was made by Kathleen Parks who described how alcohol consumption affected women's responses to a male confederate's behavior in a simulated bar setting. The fourth presentation was made by Jeanette Norris who found that alcohol and expectancies affected men's self‐reported likelihood of acting like a hypothetical sexually aggressive man. Susan E. Martin discussed the implications of these studies and made suggestions for future research.
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.
College Binge Drinking: What Is It? Who Does It?
Authors: Lange James E. , Clapp John D. , Turrisi Rob , Reavy Racheal , Jaccard James , Johnson Mark B. , Voas Robert B. , Larimer Mary
Published: April 2006

This article presents research included in the symposium at the 2001 Research Society on Alcoholism meeting in Montreal, Canada. James Lange was the organizer and provided the introduction of this article. Gayle Boyd was the chairperson, and Mary Larimer was the discussant. The presentations were (1) Defining binge‐drinking quantities through resulting BACs, by James E. Lange and Robert B. Voas; (2) Environmental predictors of heavy episodic drinking events, by John D. Clapp; (3) Parents’ continuing role in college binge drinking, by Rob Turrisi, Racheal Taki, and James Jaccard; and (4) Motivations of binge drinkers, by Mark B. Johnson, Robert B. Voas, and James E. Lange. The summary and discussion were provided by Mary Larimer.
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.
Kindling of Withdrawal: A Study of Craving and Anxiety After Multiple Detoxifications in Alcoholic Inpatients
Authors: Duka Theodora , Townshend Julia M. , Collier Kirsty , Stephens David N.
Published: April 2006

Background: The increased severity of withdrawal during successive detoxifications from alcohol is well documented for seizures, but the importance of the number of withdrawal events for other withdrawal symptoms such as anxiety and for alcohol craving is not known. Studies in animals are consistent with increases in reinforcing properties of alcohol with a greater number of withdrawal experiences. Thus, we predicted that patients who had undergone multiple detoxifications would show greater desire for alcohol and might experience more anxiety compared with patients with fewer detoxifications or compared with social drinkers.

Methods: Forty‐two alcoholic inpatients were divided on the basis of medically supervised detoxifications into HI‐med (more than two previous detoxifications, n= 6) and LO‐med (two or fewer previous detoxifications, n= 36) and compared with a group of social drinkers matched for age, sex, and verbal IQ (n= 43). An additional analysis was performed by dividing the participants into HI‐total (n= 22) and LO‐total (n= 20) previous detoxification groups (three or more and less than three previous detoxifications, respectively) by using all previous detoxifications, which included unsupervised attempts. Anxiety was measured by Spielberger's State‐Trait Anxiety Inventory; mood was evaluated by using the Profile of Mood States; craving was evaluated with a short version of the Desire for Alcohol Questionnaire; and an emotional Stroop test was used that employed positive, negative, and alcohol‐related words.

Results: When the analysis was based on the medically supervised detoxifications only, alcoholic participants (HI‐ and LO‐med) had higher ratings in trait anxiety and in feelings of anger, anxiety, depression, and confusion, but also friendliness; had higher craving ratings; and made more errors in the alcohol Stroop compared with social drinkers. In addition, the number of errors in the emotional Stroop for negative words was higher in the group with the higher number of detoxifications. When we analyzed the total number of detoxifications, this effect for the emotional Stroop errors was no longer seen. Instead, ratings of anger in the Profile of Mood States were greater in the HI‐total compared with the LO‐total detoxification group. These effects remained when the correlates alcohol consumption and degree of dependency were introduced as covariates, which showed that the effects found are probably attributable to the number of withdrawals.

Conclusions: These data suggest that for inpatients with short history of alcoholism, the consequences of multiple withdrawals may not relate to anxiety or craving.
Temporal Discrimination Learning in Abstinent Chronic Alcoholics
Authors: McGlinchey‐Berroth Regina , Fortier Catherine B. , Cermak Laird S. , Disterhoft John F.
Published: April 2006

Background: Converging evidence from varied experimental paradigms has demonstrated that the cerebellum is involved in the timing of learned behavior. Given the documented neurological changes secondary to chronic alcoholism, particularly cerebellar degeneration, the ability of recovered chronic alcoholics to learn a temporal discrimination was assessed by using delayed eyeblink classical conditioning.

Methods: Twelve abstinent alcoholic participants and 12 matched control participants were randomly presented 2 clearly discriminable tone conditioned stimuli that were individually paired with 2 different interstimulus intervals.

Results: The data revealed a significant alteration in the abstinent alcoholics’ peak latency measure at the long interstimulus intervals and an overall impairment in their level of acquisition of conditioned responses. No group differences in extinction were observed.

Conclusions: It was speculated that cerebellar cortical atrophy caused by years of alcohol abuse resulted in the peak latency alteration and that atrophy extending into deep cerebellar nuclei caused the overall impairment in conditioned response acquisition.
Role of Acetaldehyde in the Discriminative Stimulus Effects of Ethanol
Authors: Quertemont Etienne , Grant Kathleen A.
Published: April 2006

Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase inhibitor 3‐amino‐1,2,4‐triazole (AT) reduces the production of acetaldehyde, and AT administration can reduce a number of ethanol‐induced behavioral effects; this suggests the involvement of acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating the discriminative stimulus effects of ethanol remains unclear.

Methods: The contribution of acetaldehyde to the discriminative stimulus effects of ethanol was investigated by use of a two‐lever drug discrimination paradigm with food reinforcement. Male Long‐Evans rats were trained to discriminate water from either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with ethanol (0–2.5 g/kg by gavage) and acetaldehyde (0–300 mg/kg intraperitoneally). A cumulative dose‐response procedure was then used to investigate the effects of pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol discrimination.

Results: Acetaldehyde up to doses that decreased response rates (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or 2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose‐response curves for ethanol discrimination.

Conclusions: These results show that exogenous acetaldehyde administration does not produce discriminative stimulus effects that are similar to those of ethanol. Also, pretreatment with the catalase inhibitor did not affect the dose‐response curve for ethanol discrimination, and this suggests that endogenously produced acetaldehyde does not contribute to the discriminative stimulus effects of ethanol. Together these results suggest that acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0 g/kg ethanol.
Effects of Stress and Alcohol on Subjective State in Humans
Authors: Söderpalm Anna H. V. , de Wit Harriet
Published: April 2006

Background: There is increasing evidence that stress and hypothalamic‐pituitary‐adrenal axis activation interact with drugs of abuse and influence drug‐taking behaviors. Both studies with laboratory animals and survey data with alcohol users suggest that acute or chronic stressful events increase alcohol intake. One mechanism for the increase in alcohol intake may be that stress alters the subjective effects produced by the drug in ways that enhance the reinforcing properties of alcohol. Therefore, in this study we determined whether an acute social stressor alters subjective responses to ethanol in humans. The stressor was a modified version of the Trier Social Stress Test, an arithmetic task that increases cortisol levels.

Methods: Twenty male volunteers participated in two laboratory sessions, in which they performed the Trier Social Stress Test on one session and no task on the other session, immediately before consuming a beverage that contained ethanol (0.8 g/kg in juice) or placebo (juice alone). Eleven subjects received ethanol on both sessions, and nine subjects received placebo on both sessions. Primary dependent measures were self‐report questionnaires of mood states. Salivary levels of cortisol were obtained to confirm the effectiveness of the stress procedure.

Results: Stress alone produced stimulant‐like subjective effects. In the group who received ethanol, stress increased sedative‐like effects and decreased stimulant‐like effects.

Conclusions: At this relatively high dose of ethanol, stress increased sedative effects of alcohol and did not increase desire for more alcohol. It is possible that in some individuals, the increased sedative effects after stress may increase the likelihood of consuming more alcohol. The effects of stress on consumption at this, or lower, doses of alcohol remain to be determined.
Biphasic Alcohol Response Differs in Heavy Versus Light Drinkers
Authors: King Andrea C. , Houle Tim , de Wit Harriet , Holdstock Louis , Schuster Alyson
Published: April 2006

Background: Most studies of risk factors for alcohol‐related problems have focused on biological family history as a primary risk factor. However, other factors, such as early‐age heavy drinking, are also risk factors for sustained or progressive heavy consumption. Little is currently known about the mechanisms underlying binge or heavy drinking.

Methods: This study examined the acute subjective and objective effects of ethanol in heavy drinkers versus light drinkers. Thirty‐four subjects participated in this within‐subjects study consisting of three early‐evening testing sessions in which subjects consumed a beverage containing either 0.8 or 0.4 g/kg ethanol or placebo.

Results: Compared with lighter drinkers, heavy drinkers were more sensitive to the positive stimulant‐like effects of ethanol (p < 0.05), especially during the increasing limb of the blood alcohol curve. Heavy drinkers also showed less sedation and cortisol response after alcohol than the light drinkers (p < 0.05).

Conclusions: The results indicate that young adult binge drinkers show a biphasic alcohol response, with heightened sensitivity to stimulant‐like alcohol effects and greater tolerance to sedative alcohol effects compared with their light‐drinking counterparts.
Preoperative Evaluation of Chronic Alcoholics Assessed for Surgery of the Upper Digestive Tract
Authors: Martin M. J. , Heymann C. , Neumann T. , Schmidt L. , Soost F. , Mazurek B. , Böhm B. , Marks C. , Helling K. , Lenzenhuber E. , Müller C. , Kox W. J. , Spies C. D.
Published: April 2006

Background: Alcoholics are at risk of developing major complications in the postoperative period. Adequate prophylactic treatment, as well as preoperative abstinence, can significantly decrease the rate of complications. However, the preoperative diagnosis of alcoholism is difficult to establish. The purpose of this study was to assess whether three preoperative visits, an alcohol‐related questionnaire (CAGE), and the laboratory markers carbohydrate‐deficient transferrin (CDT) and γ‐glutamyltransferase (GGT) would increase the rate of detection of chronic alcoholics.

Methods: The study included the Departments of ENT, Facial and Maxillofacial Surgery, and General Surgery of a university hospital; 705 male patients were assessed for tumor surgery of the upper digestive tract and were allocated to 5 different groups. All patients were seen three times, and five different strategies were used to detect chronic alcoholics. The gold standard was the diagnosis of alcohol misuse made by an experienced (blinded) investigator according to the DSM‐III‐R. The main outcome measurements were the detection rates of the different test strategies.

Results: By clinical routine alone, only 16% were detected during the first visit and 34% after three visits. If the CAGE questionnaire was added, sensitivity increased to 64%. The further addition of GGT or CDT led to 80 and 85% detections, respectively. A combination of all tests had a sensitivity of 91%.

Conclusions: To detect more alcoholic patients at risk for major complications, patients should be seen more often, and additional diagnostic tools such as the CAGE, CDT, and GGT should be used before surgery.
Treating Adolescents Together or Individually? Issues in Adolescent Substance Abuse Interventions
Authors: O'Leary Tracy A. , Brown Sandra A. , Colby Suzanne M. , Cronce Jessica M. , D'Amico Elizabeth J. , Fader Jonathan S. , Geisner Irene M. , Larimer Mary E. , Maggs Jennifer L. , McCrady Barbara , Palmer Rebekka S. , Schulenberg John , Monti Peter M.
Published: April 2006

This article summarizes the proceedings of a symposium, chaired by Peter Monti and cochaired by Tracy O'Leary, that was presented at the 2001 RSA Meeting in Montreal, Quebec. The aim of this symposium was to present data on group‐ and individual‐based interventions for adolescent alcohol and substance abuse, with a discussion of the implications of research findings bearing on developmental considerations when working with adolescents and young adults. Elizabeth J. D'Amico, PhD, reviewed recent findings on adolescents' choice of type of substance abuse treatment. Jennifer L. Maggs, PhD, presented a developmental perspective on this issue. Tracy O'Leary, PhD, presented data on enhancing motivational interviewing with the presence of a supportive peer for college students cited for alcohol infractions. Mary E. Larimer, PhD, presented 1‐year follow‐up results of the Greeks 2000 Project, a 5‐year longitudinal study designed to evaluate the efficacy of an alcohol abuse prevention program provided to college students who were entering a pledge class (first year) of Greek houses. Barbara McCrady, PhD, a noted expert on the treatment of couples for substance abuse problems, served as discussant.
One Drink to a Lifetime of Drinking: Temporal Structures of Drinking Patterns
Authors: Gruenewald Paul J. , Russell Marcia , Light John , Lipton Rob , Searles John , Johnson Fred , Trevisan Maurizio , Freudenheim Jo , Muti Paola , Carosella Ann Marie , Nochajski Thomas H.
Published: April 2006

This article presents the proceedings of a symposium at the 2001 Research Society on Alcoholism Meeting in Montreal, Canada. The cochairs were Paul J. Gruenewald and Marcia Russell. The focus of the symposium was on mathematical, methodological, and statistical approaches to the assessment of drinking patterns from short (daily and monthly) to very long periods (the life course) of time. The research presented in the symposium argues that (1) model‐based approaches to analyzing drinking patterns can provide comprehensive bases for assessing drinking risks, (2) data acquisition technologies that track daily drinking over long periods of time can illuminate unique features of drinking associated with abuse and dependence, and (3) retrospective data can be used to assess life‐course trajectories of drinking associated with chronic problem outcomes. Each of the presentations points toward an integrated approach to understanding acute and chronic risks related to alcohol use. The presentations were (1) Mathematical models of current drinking, by Paul J. Gruenewald and Fred Johnson; (2) Mathematical models of drinking problems, by John Light and Rob Lipton; (3) Patterns of drinking ascertained from daily data aggregated across 24 months, by John Searles; and (4) Cognitive lifetime drinking histories and natural histories of drinking, by Marcia Russell, Paul J. Gruenewald, Fred Johnson, Maurizio Trevisan, Jo Freudenheim, Paola Muti, Ann Marie Carosella, and Thomas H. Nochajski.
The Genetics of Alcoholism in Polynesians: Alcohol and Aldehyde Dehydrogenase Genotypes in Young Men
Authors: Chambers Geoffrey K. , Marshall Stephen J. , Robinson Geoffrey M. , Maguire Sean , Newton‐Howes Jan , Chong Nicola L.
Published: April 2006

Background The last 10 years have seen growing recognition of the significance of the genes encoding enzymes responsible for hepatic alcohol metabolism as protective factors in the development of alcoholism.

Methods We have developed DNA sequencing assays for measuring genetic variation at the alcohol dehydrogenase

2 (ADH2), ADH3, and aldehyde dehydrogenase 2 (ALDH2) loci. These have been used to survey volunteer control subjects from three New Zealand ethnic groups (white, Asian, and Polynesian) and young male alcoholics recruited from white and New Zealand Maori patients in a local treatment program.

Results The allele frequency values for whites and Asians obtained in our study closely match those obtained previously in other laboratories. Our data (the first for Polynesians) are 0.42 for ADH2*2, 0.78 for ADH3*1, and 0.00 for ALDH2*2. In the New Zealand Maori alcoholic patients, the ADH2*2 frequency is significantly lower (0.15;p < 0.01). The frequency of ADH3*1 is also lower in this group (0.60), but this value is not significant (0.05 <p < 0.06).

Conclusions In young male New Zealand Maori, the ADH2*2 allele is a protective factor against alcoholism even in the absence of ALDH2*2.
The Effect of Tryptophan Depletion on Alcohol Self‐Administration in Non‐Treatment‐Seeking Alcoholic Individuals
Authors: Petrakis Ismene L. , Buonopane Alessandra , O'Malley Stephanie , Cermik Omer , Trevisan Louis , Boutros Nashaat N. , Limoncelli Diana , Krystal John H.
Published: April 2006

Background Alcohol self‐administration in the laboratory has been used to evaluate pharmacological treatments and neurobiological mechanisms that underlie alcohol use in alcohol‐dependent individuals. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the amount of alcohol consumed in a self‐administration paradigm in non‐treatment‐seeking individuals with alcohol use disorders.

Methods Individuals with alcohol dependence (n= 8) and alcohol abuse (n= 4) who were not seeking treatment were recruited by advertisement and participated in two test days, 1 week apart. Each test session was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double‐blind fashion. The test session began with a cue exposure session where subjects were exposed to their favorite alcoholic beverage and asked to rate their craving for alcohol. After this, subjects were administered a priming drink designed to raise blood alcohol levels to 0.02 g%. Subjects then had the opportunity to drink up to eight additional drinks, each designed to raise blood alcohol levels by 0.02 g%, or to receive $3 for each drink not consumed over a 2‐hr period.

Results There were no significant differences in alcohol consumed or subjective intoxication with active tryptophan depletion compared with placebo. Self‐reported craving correlated with the amount of alcohol consumed in the session.

Conclusions These data question the dependence of alcohol self‐administration on the ongoing synthesis of serotonin.
The Five‐Year Predictive Validity of Each of the Seven DSM‐IV Items for Alcohol Dependence Among Alcoholics
Authors: Schuckit Marc A. , Danko George P. , Smith Tom L. , Buckman Kelly R.
Published: April 2006

Background Information about the prognostic implications of a DSM‐IV diagnosis of alcohol dependence is important to both clinicians and researchers. In this regard, only limited data are available on the performance of specific diagnostic items.

Methods This study reports data gathered with a structured, validated interview with 642 alcohol‐dependent men and women from the Collaborative Study of the Genetics of Alcoholism (COGA). The goals were to evaluate the ability of each of the DSM‐IV dependence items to predict the occurrence over the next 5 years of a broad pattern of 27 alcohol‐related problems. For comparison, similar data are reported regarding the performance of abuse criteria for 516 additional subjects.

Results The results revealed that dependence item 3 (use of alcohol in larger amounts) was the only criterion that did not relate significantly to outcome, and indicated that the dependence criteria related relatively similarly to different types of outcomes among alcoholics. No specific combination of diagnostic items stood out in predicting outcome but, rather, the span of items generally performed well.

Conclusions These data support the potential usefulness of the DSM‐IV dependence criteria.