Low-dose Alcohol Research Articles

Low-dose chronic prenatal alcohol exposure abolishes the pro-cognitive effects of angiotensin IV

Prenatal ethanol exposure (PAE) in humans results in a spectrum of disorders including deficits in learning and memory. Animal models to date have typically used high ethanol doses but have not identified the biochemical changes underlying the cognitive deficit. This study used treatment of mouse breeding harems with 5% ethanol via drinking water throughout pregnancy and lactation and explored the behavioural consequences in the progeny at 3–6 months of age using the open field test, novel object recognition test and elevated plus maze to measure anxiety and memory consolidation. The effects of angiotensin IV on behaviour of the progeny were also determined. The results indicated that PAE increased anxiety-like behaviour as determined in the open field test in male but not female progeny. In control animals, angiotensin IV enhanced memory consolidation in males, but this effect was abolished by PAE. The abolition of the pro-cognitive effect of angiotensin IV was not a consequence of increased anxiety, and there was some evidence of a long-lasting anxiolytic effect of angiotensin IV in the male PAE progeny. These results suggest that PAE may act via alteration of the actions of the brain renin-angiotensin system to impair memory consolidation, but these effects may be partially sex-dependent.

Does familial risk for alcohol use disorder predict alcohol hangover?

AimsPositive family history of alcohol use disorder (FHP), a variable associated with propensity for alcohol use disorder (AUD), has been linked with elevated hangover frequency and severity, after controlling for alcohol use. This implies that hangover experiences may be related to AUD. However, inadequate control of alcohol consumption levels, low alcohol dose and testing for hangover during the intoxication phase detract from these findings. Here, we present further data pertinent to understanding the relationship between family history and alcohol hangover.MethodsStudy 1 compared past year hangover frequency in a survey of 24 FHP and 118 family history negative (FHN) individuals. Study 2 applied a quasi-experimental naturalistic approach assessing concurrent hangover severity in 17 FHP and 32 FHN individuals the morning after drinking alcohol. Both studies applied statistical control for alcohol consumption levels.ResultsIn Study 1, both FHP status and estimated blood alcohol concentration on the heaviest drinking evening of the past month predicted the frequency of hangover symptoms experienced over the previous 12 months. In Study 2, estimated blood alcohol concentration the previous evening predicted hangover severity but FHP status did not.ConclusionsFHP, indicating familial risk for AUD, was not associated with concurrent hangover severity but was associated with increased estimates of hangover frequency the previous year.

Modelling Rohypnol [Flunitrazepam] and Alcohol Abuse and Resultant Effects on Hippocampal Histoarchitecture and Biochemicals in Wistar Rats

Rohypnol and alcohol abuse is often reported among young people. Rohypnol is often abused voluntarily to erase memory of indulgence. It is also used in perpetuating crime such as in rape cases when the perpetrator administers certain doses of rohypnol to make the victim lose the memory of such event. Interestingly, young people often abuse alcohol and rohypnol. While the former is often used as a social drug, the latter is combined in certain instances to erase or reduce the memory of such. A number of literatures exist on the effects of alcohol on heath, brain and mind; but not a good number of investigations have considered the effects of rohypnol on hippocampal structure as well as the nature of its effects when combined with alcohol. This particular investigation is aimed at modelling rohypnol and alcohol abuse and resultant effects on hippocampal histoarchitecture and biochemicals in Wistar rats. Forty eight [n=48] adult male Wistar rats were divided into six groups, A-F. Group A served as the control Group B received the low dose of flunitrazepam; Group C received the high dose of flunitrazepam; Group D received the low dose of alcohol; Group E received the high dose of alcohol; Group F received the low dose of flunitrazepam and alcohol. Experiment lasted 21 days and animals were sacrificed by cervical dislocation. Results showed that the two substances did not produce extensive structural disruption of the hippocampus. However, specific regions of the hippocampus showed morphological aberrations, resulting in mild heterogeneity. Also, the enzyme chemistry of the hippocampus cytochrome C oxidase and G6PDH enzymes was altered.

Effects of Age and Acute Moderate Alcohol Administration on Neurophysiology During Simulated Driving.

Driver age and blood alcohol concentration are both important factors in predicting driving risk; however, little is known regarding the joint import of these factors on neural activity following socially relevant alcohol doses. We examined age and alcohol effects on brain oscillations during simulated driving, focusing on 2 region-specific frequency bands implicated in task performance and attention: parietal alpha power (PAP; 8 to 12Hz) and frontal theta power (FTP; 4 to 7Hz). Participants included 80 younger (aged 25 to 35years) and 40 older (aged 55 to 70years) community-dwelling, moderate drinkers. Participants consumed placebo, low, or moderate doses of alcohol designed to achieve target peak breath alcohol concentrations of 0, 0.04, or 0.065g/dl, respectively. Electrophysiological measures were recorded during engagement in a simulated driving task involving 4 scenarios of varied environmental complexity. A main effect of age was detected in FTP, but neither an alcohol effect nor interactions were observed. For PAP, an age-by-alcohol interaction was detected. Relative to placebo controls, older and younger participants receiving low-dose (0.04g/dl) alcohol evinced divergent PAP alterations, with a pattern of higher power among older participants and lower power among younger participants. This interaction was noted across the varied environmental contexts. These findings are consistent with the hypothesis that compared with younger individuals, older drivers may be differentially susceptible to alcohol effects. While these age-by-alcohol interactions in neural activity are provocative, further investigation exploring the mechanisms and behavioral correlates of these effects will be crucial in determining their behavioral impact.

The Effect of Alcohol on Gastrointestinal Motility.

The Gastrointestinal (GI) tract is one of the most affected systems by alcohol consumption. Alcohol can affect the esophagus in several ways: induces mucosal inflammation, increases the risk for Barrett esophagus and esophageal cancer, and also impairs the esophageal motility. Numerous studies have reported an increased prevalence of Gastroesophageal Reflux Disease (GERD) or erosive esophagitis in alcoholics. Some alcoholics exhibit an abnormality of esophageal motility known as a "nutcracker esophagus". Alcohol effect on gastric motility depends on the alcohol concentration. In general, beverages with high alcohol concentrations (i.e., above 15 percent) appear to inhibit gastric motility and low alcohol doses (wine and beer) accelerate gastric emptying. Also, acute administration of ethanol inhibits the gastric emptying, while chronic administration of a large dose of alcohol accelerates gastric motility. The effect of alcohol on small bowel motility differs according to the type of consumption (acute or chronic). Acute administration of alcohol has been found to inhibit small bowel transit and chronic administration of a large dose of alcohol accelerates small bowel transit. This article reviews some of the below findings.

Depressive Symptoms, Acute Alcohol Intoxication, and Risk Rationale Effects on Men’s Condom Use Resistance

This study examined the role of depressive symptoms, acute intoxication, and risk rationale in men’s use of condom use resistance (CUR) tactics in an experimental study. Participants included 313 heterosexual male, nonproblem drinkers, ages 21 to 30. Participants were randomized to one of four beverage conditions: no alcohol, placebo, low (.04%) alcohol dose, or high (.08%) alcohol dose. They read an eroticized scenario depicting a consensual sexual encounter with a female partner who requested a condom to prevent either pregnancy or sexually transmitted infections (STIs) (risk rationale) and then indicated their intentions to use 10 different CUR tactics. Hypotheses related to the pharmacological, dosage, and expectancy effects of alcohol were tested in a generalized linear model. In intoxicated (.04% and .08%) men who were given a pregnancy risk rationale, depressive symptoms were associated with stronger intentions to use CUR tactics than in sober (control and placebo) men. Men who received a high alcohol dose (.08%) and who were given a pregnancy risk rationale reported higher intentions to use CUR tactics than those who received a lower alcohol dose (.04%). Findings suggest that the pharmacological effects of alcohol on men’s likelihood to resist condoms vary by the saliency of the risk rationale and mood-related variables.

Intravenous self-administration of alcohol in rats-problems with translation to humans.

Alcohol is consumed orally by humans, and oral self-administration has been successfully modeled in laboratory animals. Over the last several years, attempts have been made to develop a procedure for the reliable intravenous (IV) self-administration of alcohol in rodents. IV self-administration would provide a better tool for investigating neurobiological mechanisms of alcohol reinforcement and dependence because confounding factors associated with oral self-administration, such as variations in orosensory sensitivity to alcohol and/or its absorption, are avoided. A review of the literature shows that rats, mice and non-human primates can initiate and maintain IV self-administration of alcohol. However, there are 50- to 100-fold interspecies differences in the reported alcohol infusion doses required. Most surprising is that the infusion dose (1-2 mg/kg) that reliably maintains IV alcohol self-administration in rats results in total alcohol intakes of only 20-25 mg/kg/hour, which are unlikely to have significant pharmacological effects. The evidence to support IV self-administration of such low doses of alcohol in rats as well as the potential biological mechanisms underlying such self-administration are discussed. The minute amounts of alcohol shown to reliably maintain IV self-administration behavior in rats challenge the relationship between their blood alcohol levels and the rewarding and reinforcing effects of alcohol.

Pharmacological and Expectancy Effects of a Low Amount of Alcohol Drinking on Outcome Valuation and Risk Perception in Males and Females.

The high-dose, alcohol-induced influences on risk perception and loss aversion depend on sex. On the other hand, low-dose alcohol has less effect on risky behavior. However, the effect of low-dose alcohol on subjective valuation of gain or loss and also the effect of placebo (expectancy of alcohol) on risk perception have not been fully investigated. We investigated the effects of low-dose alcohol (0.02 g/100 ml blood alcohol concentration) and placebo effects on subjective risk perception and subjective valuation of uncertain gain and loss in females and males. Participants in the control group and the placebo group were served alcohol-free, wine-flavored beverage and participants of alcohol group were served wine (14% alcohol). The placebo group was not informed that the drink was not alcohol but the control group was informed. Then paper–pencil tasks for subjective risk perception and valuation of gain or loss were performed 45 min after drinking the beverage. The participants were asked to draw the line on a 180 mm scale for each question. The placebo effects as well as the low-dose alcohol effects were observed in subjective valuations of gain or loss. Except for effect of beverages, a gender difference was also observed for subjective likelihood. The females estimated a low-probability loss as more likely and estimated a high-probability gain as less likely than did the males. From the Stevens’ law fitting analysis, the placebo, not alcohol, significantly induced the psychophysical effect of the subjective valuation of gain or loss. These results indicate that the psychological effects of expectancy of alcohol (placebo) could be a major factor in changing the subjective valuation of gain or loss over the pharmacological effects of a small amount of alcohol (like a glass of wine). Furthermore, these results also indicate that gender differences should be taken into account when investigating pharmacological or psychological effect on decision-making.

Transcatheter Alcohol-Mediated Perivascular Renal Denervation With the Peregrine System: First-in-Human Experience.

This study evaluated the first clinical use of a new endovascular approach to renal denervation, using chemical neurolysis, via periadventitial infusion of dehydrated alcohol (ethanol) to perform "perivascular" renal artery sympathetic denervation. Renal denervation remains a promising technology for the treatment of hypertension and other disorders. A novel 3-needle delivery device (Peregrine System Infusion Catheter, Ablative Solutions, Inc., Kalamazoo, Michigan) was introduced into the renal arteries of 18 subjects with refractory hypertension. Microdoses of alcohol were infused bilaterally via the 3 needles into to the adventitial space (0.30 ml/artery, 37 arteries). Renal artery angiography was performed at the time of the procedure and at 6 months (n = 16). The primary safety endpoints were complications associated with the catheter insertion and delivery of the neurolytic agent or any major vascular access complications. The secondary performance endpoint was a reduction in office-based systolic blood pressure at 6 months compared with baseline. Procedural success was achieved in 100% of subjects (N = 18) and arteries (N = 37). There were no study-related adverse clinical events at follow-up. One death of a subject was recorded but determined by the investigator and an independent medical monitor to be non-study related. There were no angiographic observations of renal artery stenosis, aneurysms, or other renal artery abnormalities at 6 months (32 renal arteries). Sixteen of the 18 subjects had a 6-month follow-up. The mean office systolic blood pressure decreased from 175 ± 17 mm Hg to 151 ± 26 mm Hg (-24 mm Hg). There was an average reduction of antihypertensive medications from 3.4 (baseline) to 2.0 per subject at 6 months. Chemical renal denervation using the infusion of very low doses of alcohol directly into the adventitial space appears to be feasible and safe. This approach may be a promising alternative approach to perform catheter-based renal denervation. These results need to be confirmed in larger scale clinical studies.

Cannabis effects on driving longitudinal control with and without alcohol.

Although evidence suggests cannabis impairs driving, its driving-performance effects are not fully characterized. We aimed to establish cannabis' effects on driving longitudinal control (with and without alcohol, drivers' most common drug combination) relative to psychoactive ∆(9) -tetrahydrocannabinol (THC) blood concentrations. Current occasional (≥1×/last 3 months, ≤3 days per week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500 mg placebo, low (2.9%), or high (6.7%) THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject, six conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives 0.5-1.3 h post-inhalation. Blood and breath alcohol samples were collected before (0.17 and 0.42 h) and after (1.4 and 2.3 h) driving. We evaluated the mean speed (relative to limit), standard deviation (SD) of speed, percent time spent >10% above/below the speed limit (percent speed high/percent speed low), longitudinal acceleration, and ability to maintain headway relative to a lead vehicle (headway maintenance) against blood THC and breath alcohol concentrations (BrAC). In N=18 completing drivers, THC was associated with a decreased mean speed, increased percent speed low and increased mean following distance during headway maintenance. BrAC was associated with increased SD speed and increased percent speed high, whereas THC was not. Neither was associated with altered longitudinal acceleration. A less-than-additive THC*BrAC interaction was detected in percent speed high (considering only non-zero data and excluding an outlying drive event), suggesting cannabis mitigated drivers' tendency to drive faster with alcohol. Cannabis was associated with slower driving and greater headway, suggesting a possible awareness of impairment and attempt to compensate. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Blood Collection Time on Measured Δ9-Tetrahydrocannabinol Concentrations: Implications for Driving Interpretation and Drug Policy.

In driving-under-the-influence cases, blood typically is collected approximately 1.5-4 h after an incident, with unknown last intake time. This complicates blood Δ(9)-tetrahydrocannabinol (THC) interpretation, owing to rapidly decreasing concentrations immediately after inhalation. We evaluated how decreases in blood THC concentration before collection may affect interpretation of toxicological results. Adult cannabis smokers (≥1×/3 months, ≤3 days/week) drank placebo or low-dose alcohol (approximately 0.065% peak breath alcohol concentration) 10 min before inhaling 500 mg placebo, 2.9%, or 6.7% vaporized THC (within-individuals), then took simulated drives 0.5-1.3 h postdose. Blood THC concentrations were determined before and up to 8.3 h postdose (limit of quantification 1 μg/L). In 18 participants, observed Cmax (at 0.17 h) for active (2.9 or 6.7% THC) cannabis were [median (range)] 38.2 μg/L (11.4-137) without alcohol and 47.9 μg/L (13.0-210) with alcohol. THC Cmax concentration decreased 73.5% (3.3%-89.5%) without alcohol and 75.1% (11.5%-85.4%) with alcohol in the first half-hour after active cannabis and 90.3% (76.1%-100%) and 91.3% (53.8%-97.0%), respectively, by 1.4 h postdose. When residual THC (from previous self-administration) was present, concentrations rapidly decreased to preinhalation baselines and fluctuated around them. During-drive THC concentrations previously associated with impairment (≥8.2 μg/L) decreased to median <5 μg/L by 3.3 h postdose and <2 μg/L by 4.8 h postdose; only 1 participant had THC ≥5 μg/L after 3.3 h. Forensic blood THC concentrations may be lower than common per se cutoffs despite greatly exceeding them while driving. Concentrations during driving cannot be back-extrapolated because of unknown time after intake and interindividual variability in rates of decrease.

Low-Dose Alcohol Effects on Measures of Inhibitory Control, Delay Discounting, and Risk-Taking

The per se limit for alcohol intoxication in the USA is a blood alcohol concentration (BAC) of 80 mg/100 ml. However, there is abundant evidence that skilled performance (e.g., information processing, motor coordination) is impaired at BACs well below this limit. By contrast, less is known regarding low-dose alcohol effects on impulsivity-related behaviors, including inhibitory control, delay discounting, and risk-taking. Here, we review the evidence to date regarding performance on behavioral impulsivity and decision-making tasks at BACs below the 80 mg/100 ml limit. Overall, below-limit doses of alcohol impair inhibitory control and increase risk-taking but do not affect delay discounting. Within each facet, alcohol effects were largely task-dependent. We discuss the results in relation to above-limit alcohol effects on these measures, as well as implications of these findings in terms of disadvantageous behavior at BACs below the legal level of intoxication.

Potentiation of amygdala AMPA receptor activity selectively promotes escalated alcohol self-administration in a CaMKII-dependent manner.

Growing evidence indicates that drugs of abuse gain control over the individual by usurping glutamate-linked mechanisms of neuroplasticity in reward-related brain regions. Accordingly, we have shown that glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity in the amygdala is required for the positive reinforcing effects of alcohol, which underlie the initial stages of addiction. It is unknown, however, if enhanced AMPAR activity in the amygdala facilitates alcohol self-administration, which is a kernel premise of glutamate hypotheses of addiction. Here, we show that low-dose alcohol (0.6 g/kg/30 minutes) self-administration increases phosphorylation (activation) of AMPAR subtype GluA1 S831 (pGluA1 S831) in the central amygdala (CeA), basolateral amygdala and nucleus accumbens core (AcbC) of selectively bred alcohol-preferring P-rats as compared with behavior-matched (non-drug) sucrose controls. The functional role of enhanced AMPAR activity was assessed via site-specific infusion of the AMPAR positive modulator, aniracetam, in the CeA and AcbC prior to alcohol self-administration. Intra-CeA aniracetam increased alcohol-reinforced but not sucrose-reinforced responding and was ineffective following intra-AcbC infusion. Because GluA1 S831 is a Ca2+/calmodulin-dependent protein kinase II (CaMKII) substrate, we sought to determine if AMPAR regulation of enhanced alcohol self-administration is dependent on CaMKII activity. Intra-CeA infusion of the cell-permeable CaMKII peptide inhibitor myristolated autocamtide-2-related inhibitory peptide (m-AIP) dose-dependently reduced alcohol self-administration. A subthreshold dose of m-AIP also blocked the aniracetam-induced escalation of alcohol self-administration, demonstrating that AMPAR-mediated potentiation of alcohol reinforcement requires CaMKII activity in the amygdala. Enhanced activity of plasticity-linked AMPAR-CaMKII signaling in the amygdala may promote escalated alcohol use via increased positive reinforcement during the initial stages of addiction.

The effect of acute alcohol on motor-related EEG asymmetries during preparation of approach or avoid alcohol responses

Alcohol-approach tendencies have been associated with heavy drinking and play a role in the transition to alcohol abuse. Such cognitive biases might predict future alcohol use better under a low dose of alcohol. The aim of this prospective study was to investigate both the magnitude and the predictive power of alcohol-induced changes on approach-avoidance bias and bias-related cortical asymmetries during response preparation across heavy and light drinking adolescents. In heavy drinking adolescents greater approach-related asymmetry index in the beta-band was observed for soft-drink cues compared to alcohol ones and this increase was associated with increase in difficulty to regulate alcohol intake. Earlier findings demonstrated that young heavy drinkers hold both positive and negative implicit alcohol associations, reflecting an ambiguity towards alcohol. The increase in approach related beta-lateralization for soft-drink cues measured in this study may represent a compensatory effort for the weaker S–R mapping (approaching soft drink). The MRAA findings in this study may highlight a mechanism related to overcompensation due to ambivalent attitudes towards drinking in our heavy drinking sample who had greater problems to limit their alcohol intake compared to light drinkers. Moreover, a relatively strong approach soft-drink and weak approach alcohol reaction-time bias after alcohol predicted decreasing drinking; suggesting that the capacity to control the bias under alcohol could be a protective factor.

Dose-dependent effects of alcohol administration on behavioral profiles in the MCSF test.

The acute effects of alcohol administration are age-, dose-, time- and task-dependent. Although generally considered to be a sedative drug, alcohol has both stimulatory and depressant effects on behavior, depending on dose and time. Alcohol-induced motor activating effects are consistently shown in mice but rarely demonstrated in adult, outbred rats using conventional behavioral tests. The aim of the present experiment was to study acute alcohol-induced effects on behavioral profiles in a more complex environment using the novel multivariate concentric square field™ (MCSF) test, designed for assessing different behaviors in the same trial including locomotor activity. Adult male Wistar rats (Sca:WI) were administered one intraperitoneal (i.p.) injection of alcohol (0.0 g/kg, 0.5 g/kg, 1.0 g/kg, or 1.5 g/kg) 5 min prior to the 30-min MCSF test. The two highest doses induced marked motor-suppressing effects. A significant interaction between group and time was found in general activity when comparing rats exposed to alcohol at 0.0 g/kg and 0.5 g/kg. In contrast to the 0.0 g/kg dose that increased the activity over time, animals administered the low dose (0.5 g/kg) demonstrated an initial high activity followed by a decline over time. No indications for acute alcohol-induced anxiolytic-like effects were found. The multivariate setting in the MCSF test appears to be sensitive for detecting motor-activating effects of low doses of alcohol as well as reduced locomotion at doses lower than in other behavioral tasks. The detection of subtle changes in behavior across time and dose is important for understanding alcohol-induced effects. This approach may be useful in evaluating alcohol doses that correspond to different degrees of intoxication in humans.

Alcohol Doesn't Always Compromise Cognitive Function: Exploring Moderate Doses in Young Adults.

The purpose of this study was to clarify inconsistent findings regarding the acute cognitive effects of subintoxicating alcohol doses (i.e., <80 mg/dl) by controlling for and evaluating variables that might modulate dose-related outcomes. The current study examined the effects of sex/gender and alcohol concentration on select cognitive functions in 94 individuals (49 men) between 25 and 35 years of age. Participants were randomly assigned to one of three dose conditions: target peak breath alcohol concentration of 0 mg/dl (placebo), 40 mg/dl (low), or 65 mg/dl (moderate). After beverage consumption, they completed tasks assessing psychomotor, set-shifting, and working memory ability. Analyses revealed no significant effect of dose for any cognitive domain. A trend-level effect of dose on psychomotor performance was observed, with the low-dose group performing somewhat better than the moderate-dose and placebo groups. No sex main effects or interactions were revealed. Consistent with our previous studies, these data suggest that low and moderate doses of alcohol may not compromise cognitive ability in non-problem drinkers under certain task conditions. Given the outcomes, sex differences cannot be meaningfully addressed. Future consideration of potentially influential variables and assessment of similarly well-defined cohorts might yield a clearer interpretation of alcohol's behavioral consequences.

Health benefits from moderate drinking: a critical review

Although alcohol consumption is a leading cause of preventable death and social problems worldwide, many studies have found an association between low-dose consumption and reduced risk of cardiovascular (CVD) disease. Despite important limitations in the underlying research, this idea has been promoted extensively, used to argue against the adoption of effective alcohol policies and led some doctors to advise patients to drink for better health. There are a number of grounds for scepticism about these claims. There have been no randomised studies of low-dose alcohol consumption with disease or death outcomes to confirm findings from non-randomised studies. There are many methodological problems with observational studies, most importantly confounding and misclassification. In contrast to observational studies, a recent large Mendelian randomisation study found that having a genetic disposition that causes less drinking was associated with a significantly reduced risk of coronary disease, even among those who consume modest amounts of alcohol. Recent research has also challenged some of the purported mechanisms for the protective effect of moderate drinking, eg the effect on and impact of blood lipids. This paper will provide methodological critique of the scientific basis for the claim that low-dose alcohol confers health benefits. It is concluded that the protective effects of moderate drinking may be spurious. Governments should strengthen effective alcohol control policies to reduce alcohol-related deaths, social problems and economic costs. Physician advice to patients should focus on reducing consumption among current drinkers, and should discourage drinking initiation or increased consumption on the basis of health-related considerations.

Moderate in utero alcohol exposure results in sex-dependent inflammation in the developing rat brain

Activation of the developing immune system can lead to changes in neural development and long-term neural function. Recent studies show alcohol can activate the immune system; however, fetal neuroimmune response and long-term effects of in utero alcohol exposure are unknown. This project aimed to determine how prenatal alcohol exposure affects the fetal brain and long-term immune and cognitive function. Pregnant Sprague–Dawley rats were left undisturbed or gavaged with either water or 50% ethanol, twice daily on embryonic (E) days 10–16. This low dose of alcohol resulted in a 0.08% blood alcohol concentration for 8 h. We found increased expression of TNF-alpha, TNF-SF13, TNF-SF13B, CCL2, and CCL20 in the hippocampus-cortex of E17 alcohol-exposed females, while alcohol-exposed males exhibited decreased expression of CCL2 and CCL20 chemokines. In a second experiment, using the same paradigm, pups were raised to adulthood to examine long-term learning and immune function. Learning was assessed using a novel object recognition task (NOR) and context pre-exposure facilitation effect (CPFE). We found alcohol-exposed males exhibited learning deficits in NOR following a second-immune challenge with lipopolysaccharide (LPS) immediately after pre-exposure to the objects. Additionally, alcohol-exposed males exhibited a stronger neuroimmune response to LPS in adulthood, which may precipitate cognitive deficits seen in the NOR. These studies contribute to our understanding of the impact of in utero alcohol exposure on the developing brain and immune system.

Ethanol during adolescence decreased the BDNF levels in the hippocampus in adult male Wistar rats, but did not alter aggressive and anxiety-like behaviors.

To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers. Groups of male Wistar rats (mean weight 81.4 g, n = 36) were housed in groups of four until postnatal day (PND) 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16), 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12), or water (n = 12) every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test) and anxiety-like behaviors (elevated plus maze) during adulthood. Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex. Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.

Alcohol and violence: neuropeptidergic modulation of monoamine systems.

Neurobiological processes underlying the epidemiologically established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals who are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption.