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Background: While it is well established that Roux-en-Y gastric bypass (RYGB) causes a rapid and heightened peak blood alcohol concentration (BAC), results from previous studies on the effects of sleeve gastrectomy (SG) on alcohol pharmacokinetics are conflicting. Data from 2 studies found SG did not affect BAC, whereas another study found SG caused a heightened peak BAC after alcohol ingestion. Moreover, these 3 studies estimated BAC from breathalyzers, which might not reliably estimate peak BAC., Objectives: The aims of this study were to evaluate (1) the effect of SG, relative to RYGB and a presurgery group, on alcohol pharmacokinetics and subjective effects, and (2) whether breathalyzers are reliable in this population., Setting: Single-center prospective nonrandomized trial., Methods: We performed alcohol challenge tests in 11 women who had SG surgery 1.9 ± .1 years ago (body mass index = 35.1 ± 6.6 kg/m 2 ), 8 women who had RYGB surgery 2.2 ± .4 years ago (body mass index = 30.0 ± 5.2 kg/m 2 ), and 9 women who were scheduled for bariatric surgery (body mass index = 44.1 ± 4.0 kg/m 2 ). BACs were estimated from breath samples and measured by gas chromatography at various times after consuming approximately 2 standard drinks., Results: BAC increased faster, peak BAC was approximately 2-fold higher, and feelings of drunkenness were heightened in both SG and RYGB groups relative to the presurgery group (P values<.001). BAC estimated from breath samples underestimated BAC by 27% (standard deviation = 13%) and missed peak BACs postsurgery., Conclusions: SG, similar to RYGB, causes marked alterations in the response to alcohol ingestion manifested by a faster and higher peak BAC. The breathalyzer is invalid to assess effects of gastric surgeries on pharmacokinetics of ingested alcohol., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Prior research revealed that breast stimulation altered the way the lactating body handles alcohol. Its effects depended upon when it occurred relative to drinking. The goal of the present study was to determine whether breast pumping works independently of the physiological and metabolic changes that accompany lactation. To this end, we tested 12 women when they were exclusively breastfeeding 3-5-month-old infants and then again several months after lactation had ceased. Subjects were randomly assigned to one of two groups that differed in the timing of breast pumping relative to drinking a 0.4g/kg dose of alcohol: one group breast pumped 0.6h after drinking (pumped after group) and the other pumped 1h before drinking (pumped before group). For each reproductive stage, subjects were tested on 2 separate days, consuming a standardized meal 1 h before drinking during 1 test day and remaining fasted during the other. Breath alcohol concentrations (BrAC) and temperature readings were obtained before and at fixed intervals after drinking. Pumping before drinking significantly decreased BrAC during both reproductive stages, whereas pumping after drinking resulted in different BrAC time curves during lactation when compared with after lactation. That is, levels were significantly lower during the descending phase of the time curve during than after lactation. The interactions between pumping and reproductive stage were most apparent during fed condition. Furthermore, women were more sensitive to hypothermic effects of both fasting and drinking alcohol during lactation. These findings add to the growing literature that lactating women metabolize alcohol differently, in part, due to the frequent breast stimulation during breastfeeding and the pronounced physiological changes that accompany one of the most energetically costly mammalian activities., (2010 Elsevier Inc. All rights reserved.)

This study tested two hypotheses. First, that breast pumping contributes to the previously observed decrease in ethanol bioavailability in lactating women. Second, that the effects of breast pumping are more pronounced when ethanol is consumed after a meal. The within-subject factor was test condition (fed or fasted) and the between-subject factor was experimental group (pumped before, PB; pumped after, PA). Those randomly assigned to the PB group (N = 8) breast pumped 1 h before drinking, whereas those assigned to the PA group (N = 8) breast pumped 0.6 h after drinking. Pumping before drinking significantly decreased blood ethanol concentration (P < 0.05) and ethanol bioavailability (P = 0.05). Pumping after drinking sped up elimination (P = 0.008), attenuated ethanol-induced hypothermia (P = 0.002), and increased feelings of stimulation (P = 0.03). The effects were more pronounced when ethanol was consumed after a meal. Common neural/hormonal responses to food and suckling may contribute additive effects in altering the pharmacokinetics/pharmacodynamics of ethanol, and perhaps of other drugs, during lactation.

Background: Given the physiological adaptations of the digestive system during lactation, the present study tested the hypothesis that lactation alters alcohol pharmacokinetics., Methods: Lactating women who were exclusively breastfeeding a 2- to 5-month-old infant and 2 control groups of nonlactating women were studied. The first control group consisted of women who were exclusively formula-feeding similarly aged infants, whereas the other consisted of women who had never given birth. A within-subjects design study was conducted such that women drank a 0.4 g/kg dose of alcohol following a 12-hour overnight fast during one test session (fasted condition) or 60 minutes after consuming a standard breakfast during the other (fed condition). Blood alcohol concentration (BAC) levels and mood states were obtained at fixed intervals before and after alcohol consumption., Results: Under both conditions, the resultant BAC levels at each time point were significantly lower and the area under the blood alcohol time curve were significantly smaller in lactating women when compared with the 2 groups of nonlactating women. That such changes were due to lactation per se and not due to recent parturient events was suggested by the finding that alcohol pharmacokinetics of nonlactating mothers, who were tested at a similar time postpartum, were no different from women who had never given birth. Despite lower BAC levels in lactating mothers, there were no significant differences among the 3 groups of women in the stimulant effects of alcohol. However, lactating women did differ in the sedative effects of alcohol when compared with nulliparous but not formula-feeding mothers. That is, both groups of parous women felt sedated for shorter periods of time when compared with nulliparous women., Conclusions: The systemic availability of alcohol was diminished during lactation. However, the reduced availability of alcohol in lactating women did not result in corresponding changes in the subjective effects of alcohol.

The present study was designed to determine the short-term effects of alcohol consumption on hormonal responses and mood states in nulliparous women who have regular menstrual cycles. To this aim, we conducted a within-subjects design study in which eight women consumed a 0.4-g/kg dose of alcohol in orange juice during one test session (alcohol condition) and an equal volume of orange juice (control condition) during the other. Changes in plasma prolactin, oxytocin and cortisol levels, blood alcohol concentrations (BACs), and mood states were compared. BAC peaked at approximately 36.7+5.4 min after the consumption of the alcoholic beverage and decreased thereafter. Alcohol consumption significantly increased the area under the concentration-time curve (AUC) of prolactin (P<.01) and decreased the oxytocin AUC (P=.04) when compared to the control condition. Cortisol AUCs were not different across the two experimental conditions. Similar to that previously observed in lactating women, changes in prolactin and oxytocin paralleled changes in feelings of drunkenness. The magnitude and persistence of the alcohol-induced hormonal changes in nulliparous women were significantly less pronounced than those observed in lactating women, further highlighting the dynamics of the system under study during lactation.

Background: Preweanling rats detect ethanol (175 mg/100 ml) in maternal milk when the dam is moderately intoxicated. Repeated experiences with the intoxicated dam facilitate subsequent recognition of ethanol's chemosensory attributes and promote ethanol-related memories with a negative hedonic content. This memory has been attributed to the infant's acquired association between ethanol's chemosensory attributes and its disruptive effects on maternal care. In this study, infant and adolescent ethanol intake patterns were analyzed as a function of prior interactions, during early infancy, with their intoxicated dams., Methods: During postpartum days 3, 5, 7, 9, 11, and 13, breast-feeding dams received an intragastric administration of either 2.5 g/kg of ethanol or water. Pups whose dams had been given one of these two maternal treatments were tested on postnatal day 15 for ingestion of 0% (water), 2.5, 5.0, or 10% v/v ethanol solution. During adolescence, remaining animals from these litters were first adapted to ingest water from drinking tubes and then were given simultaneous access to tap water and a given ethanol solution. The first day, a 3% v/v ethanol solution was used. This solution was increased by 1% ethanol each following day until the solution was 6% v/v ethanol., Results: Maternal drug treatment did not affect the body weights of dams, infants, or adolescents. Water intake during infancy and adolescence also was unaffected by prior maternal treatment. However, infants that had previously interacted with ethanol-intoxicated dams exhibited heightened ethanol intake scores (grams per kilogram and percentage body weight gains), especially when tested with 5 or 10% v/v ethanol solutions. Similarly, adolescent males (but not females) that had interacted with an intoxicated dam during infancy also had higher ethanol consumption levels than those that had interacted with a nonintoxicated dam., Conclusions: Contrary to what might be expected in animals that acquire an aversive memory for ethanol's chemosensory cues as a function of prior interactions with an intoxicated mother, these results indicate that such interactions promote a long-lasting increase in ethanol intake. These results suggest that rats reared by intoxicated dams become sensitive to the negative reinforcing properties of ethanol., (Copyright 2004 Research Society on Alcoholism)

Background: Fetuses learn about ethanol odor when the drug is present in the amniotic fluid. Prenatal learning comprising ethanol's chemosensory cues also suggests an acquired association between ethanol's chemosensory and postabsorptive properties. Ethanol-related thermal disruptions have been implicated as a significant component of the drug's unconditioned properties. In the present study, ethanol-induced thermal changes were analyzed in pregnant rats subjected to a moderate ethanol dose. This thermal response was later tested for its correlation with the responsiveness of the progeny to ethanol and nonethanol chemosensory stimuli., Methods: During gestational day (GD) 14, pregnant rats were subjected to a minor surgical procedure to place a subcutaneous telemetric thermal sensor in the nape of the neck. During GDs 17 to 20, females received a daily intragastric administration of ethanol (2 g/kg) or water, using solutions kept at room temperature. Maternal body temperatures were recorded before and after (4 consecutive hours) the administration of water or ethanol. Newborns representative of both prenatal treatments were tested in terms of behavioral activity elicited by the smell of ethanol or of a novel odorant (cineole). A third group of pups were tested in response to unscented air stimulation., Results: Ethanol administration during late gestation induced reliable maternal hypothermia, a thermal disruption greater than that observed in water-treated females. It was systematically observed that maternal ethanol-induced hypothermia negatively correlated with neonatal motor reactivity elicited by ethanol olfactory stimulation. No other significant correlations were observed in terms of responsiveness to cineole or to unscented air in animals prenatally exposed to ethanol or water., Conclusions: In conjunction with prior research, the present results indicate that fetal ethanol exposure may yield learning of an association between ethanol's sensory and unconditioned properties. Ethanol-induced hypothermia during late gestation seems to represent a significant component of ethanol's unconditioned consequences. Specifically, ethanol-related thermal disruptions in the womb are highly predictive of neonatal responsiveness to ethanol's chemosensory cues that are known to be processed by the near-term fetus.

Background: Preweanling rats exhibit clear behavioral signs of distress after interacting with an alcohol-intoxicated dam. Interestingly, behavioral reactivity of infants to the experience of alcohol in the nursing context decreases as a function of repeated alcohol administrations to the mother. In this study, maternal activities were examined when dams were exposed to repeated administrations of a subnarcoleptic alcohol dose. Maternal changes in alcohol metabolism were also analyzed as a function of repeated exposures to the drug., Methods: During postpartum days 3, 5, 7, 9, 11, and 13, nursing dams received an intragastric administration of either 2.5 g/kg of alcohol or water. Maternal behaviors were evaluated (experiment 1). Blood alcohol levels (BALs) of the dams were determined on postpartum day 16 after all mothers received either an intragastric (experiment 2) or an intraperitoneal (experiment 3) dose of alcohol. The doses used (2.5 g/kg intragastrically and 1.5 g/kg intraperitoneally) were chosen because they promote similar peak BALs in dams naive to alcohol., Results: Maternal behaviors were strongly affected by the state of intoxication. Nevertheless, these disruptions clearly subsided with progression of alcohol-related experiences (experiment 1). Chromatographic analysis of alcohol metabolism indicated the development of tolerance in dams that had prior experience with alcohol (experiment 2). Changes in BALs as a function of prior experience with alcohol seemed related to first-pass alcohol metabolism rather than hepatic oxidative processes of the drug (experiments 2 and 3)., Conclusions: When the dam first experiences a moderate state of alcohol intoxication, maternal behaviors are uniformly disrupted. Subsequent exposures to alcohol lead to maternal metabolic tolerance. In conjunction with previous studies, these data indicate that infantile reactivity to alcohol is dependent on how the members of the dam/pup dyad express or perceive ethanol's postabsorptive effects.

Background: Infant rats detect small amounts of alcohol (175 mg%) that are present in maternal milk whenever the dam is moderately intoxicated with alcohol. Interaction with an alcohol-intoxicated mother during the first 2 weeks of life facilitates the preweanling's subsequent discrimination of alcohol's orosensory attributes and produces conditioned aversion to alcohol. The present study further analyzed the hedonic content of infantile alcohol memories established in the nursing context by testing the interaction between experiences with an alcohol-intoxicated dam and learning procedures aimed at establishing an appetitive conditioned response toward alcohol., Methods: Experiment 1 was to determine appropriate parameters to establish a reliable conditioned preference for alcohol in 16-day-old infants. For conditioning, intraorally infused sucrose solution (appetitive reinforcer) was paired with alcohol's orosensory cues derived from an acute state of alcohol intoxication (3 g/kg). Two control groups included an unpaired condition and a group given sucrose after water intubation. Infants then were evaluated in an alcohol intake test. Relative to control animals, a reliable conditioned preference for alcohol was registered in paired pups. In experiment 2, these conditioning procedures were applied to infant rats which, before conditioning, suckled from dams subjected to a 2.5 g/kg alcohol dose (intragastric) or from water-treated females during postpartum days 3, 5, 7, 9, 11, and 13., Results: Experiment 2 showed that maternal treatment significantly affected the establishment of conditioned preferences for alcohol. Whereas pups reared by control dams exhibited reliable appetitive conditioning to alcohol, infants raised by alcohol dams completely failed to develop appetitive conditioning., Conclusions: The present results suggest that alcohol-related memories generated via infantile interactions with an intoxicated dam counteract subsequent conditioning of alcohol ingestion. In conjunction with prior studies, it is concluded that alcohol-related nursing experiences are capable of promoting alcohol memories with a negative hedonic content.

Background: Infant rats detect the presence of alcohol in milk when the dam suffers a moderate state of alcohol intoxication. The present study examined when rat pups begin to show behavioral changes indicative of the interaction with an intoxicated dam. The study also attempted to determine if infantile experiences involving a moderately intoxicated dam result in alcohol-derived memories with a particular hedonic content., Methods: Infant rats were allowed to interact during postnatal days (PDs) 3, 5, 7, 9, 11 and 13 with alcohol-intoxicated (EtOH dose: 2.5 g/kg) or alcohol-free dams. After the interaction took place, some pups were tested in terms of ultrasonic vocalizations (USVs) and motor reactivity when isolated and placed on each of two distinctive tactile surfaces (sandpaper or soft fabric) presented in a counterbalanced order, and the second of which was always paired with ambient ethanol odor. At PD 14 pups were evaluated in terms of the preference for texture (sandpaper versus soft fabric) and odor (alcohol versus clove) as well as alcohol ingestion., Results: Very early in life (PD 3) USVs and overall activity were significantly higher in pups that had previously interacted with an intoxicated dam than in those exposed to an alcohol-free dam. Although this difference was not apparent during the following days, it was clear that a specific memory of alcohol's chemosensory cues was formed. Pups interacting with intoxicated dams followed by pairing of ethanol odor and an arousing texture (sandpaper), later avoided this texture in the preference test; pups that interacted with alcohol-free dams did not show this effect. The former animals also exhibited less consumption of alcohol than preweanlings never exposed to alcohol in the context of nursing., Conclusions: In conjunction with prior studies these results indicate that very early in ontogeny the infant processes the presence of ethanol, and perhaps its effect on its mother, within the nursing context. Under the present experimental circumstances infants appear to acquire alcohol-related information that comprises an aversive hedonic component.

Background: The aim of the present study was to analyze whether alcohol as an unconditioned stimulus is capable of supporting associative learning in near-term fetuses., Methods: In experiment 1, we determined pharmacokinetic profiles of alcohol and of an aromatic substance (cineole) in amniotic fluid and maternal blood during late gestation. The results obtained through gas chromatographic analysis allowed a second experiment in which we explicitly paired peak levels of cineole with peak levels of alcohol in amniotic fluid and blood, by intragastrically administering cineole and ethanol to the dams during gestational days 17 through 20 (paired condition). Control groups were dams given cineole 4 hr before commencement of an acute state of alcohol intoxication (long-delay group) or were only exposed to water administrations (water control group). The progeny were evaluated during postnatal day 16 in terms of behavioral responsiveness to intraorally infused solutions (cineole or alcohol presented in milk vehicle, or milk alone)., Results: Mouthing responsiveness to cineole was strongly affected by the nature of prenatal treatments. Pups in the paired prenatal condition mouthed significantly less than did long-delay and water controls. Physical and behavioral measures allowed us to reject the possibility that these effects were due to teratogenic effects of alcohol during late gestation., Conclusions: These results indicate that before birth, rat fetuses are capable of acquiring associative memories supported by the unconditioned properties of alcohol. This associative memory can be expressed during infancy through a significant reduction in mouth movements in the presence of the specific orosensory cue explicitly paired with alcohol interoceptive effects in utero.

Our previous studies indicate that rat pups are able to detect the low levels of ethanol (175 mg %) found in the milk of a moderately intoxicated dam. The present study tested the effect of infantile interactions (including suckling) with ethanol-treated mothers on later behavioral responsiveness to ethanol's sensory properties. In Experiment 1, pups suckled from dams subjected to a 2.5 g/kg ethanol dose (i.g.) or water-treated females during postnatal days (PDs) 3, 5, 7, 9, 11, and 13. During PD 15, these pups were exposed to procedures to induce a conditioned aversion to the low level of ethanol (175 mg % in water), with lithium chloride as the unconditioned stimulus. Conditioning was more effective for pups with the prior ethanol experience within the nursing context. Greater responsiveness to ethanol in milk also was found for conditioning control pups that had interacted with intoxicated dams than for those that had interacted with water-treated dams. Experiment 2 determined that interaction with an intoxicated dam was sufficient for altered responsiveness to ethanol, in that the additional conditioning procedures of Experiment 1 were not needed for the effect. Generally, a relatively brief history of infantile interaction with ethanol-intoxicated dams increased later responsiveness to ethanol's orosensory properties. The results suggest that moderately intoxicated dams within the nursing context provide information to the progeny that may lead to the establishment of ethanol-related memories.

Previous animal models testing infantile reactivity to ethanol (EtOH) in maternal milk used EtOH doses that vastly exceeded levels actually encountered in a mildly or moderately intoxicated dam. The present study assessed whether 12- and 16-day-old rats are capable of detecting EtOH in milk at levels actually recorded in an intoxicated dam. Experiment 1 determined representative levels of EtOH in maternal milk as a function of maternal intragastric administration of EtOH (0.5-3.0 g/kg). Experiment 2A assessed generalization of conditioned taste aversions accrued with a high level of EtOH (6%) in either water or milk vehicles towards lower, more representative EtOH levels obtained from Experiment 1. With body weight gain as the dependent measure, conditioned aversions to milk were evident with the milk vehicle, but there was no detection of EtOH at any level at either age. Detection of the high level of EtOH (6%) in milk, however, was observed by 16 day olds within an habituation paradigm (Exp. 2b) via cardiac and behavioral (locomotion, mouthing) indexes. In Experiment 3 application of Experiment 2's more sensitive, behavioral index to assess generalization of the conditioned taste aversions revealed detection of a lower, more representative concentration of EtOH (175 mg%) in milk in 16-day-old rats. Overall the results show that the unweaned rat is capable of detecting very low concentrations of EtOH in milk and can modify their behavior accordingly. The expression of this capability is not, however, homogeneous across different response indexes. In conjunction with prior research it is clear that the infant rat's perception of EtOH in milk, including the very low levels of EtOH found in maternal milk during mild or moderate intoxication, is a relevant experience for generating new responses towards EtOH.