• Energy Research

Ethanol drinking begins during adolescence and, particularly when occurs in a binge-like pattern, exerts lingering adverse consequences. Pre-clinical studies indicate that intermittent ethanol exposure (IEA, a model of repeated ethanol intoxication), or binge eating (BE) can increase subsequent ethanol consumption. It is unknown if the promoting effects of BE upon ethanol drinking are found in female rats and are modulated by IEA at adolescence. This study assessed interactive effects between IEA and BE, upon ethanol drinking.Female Wistar rats were given 4.0 g/kg ethanol, every other day from postnatal day 25-45. At adulthood, they were exposed to sessions in which a brief offering of a sizeable portion of highly palatable sugary pills was followed by a 120-min exposure to an ethanol bottle.Exploratory activity and recognition memory was not affected by the IEA. Glutathione peroxidase and catalase activity, and lipid peroxidation (measured in blood and brain at the end of the procedure) were not significantly affected by IEA or BE exposure. BE alone had a mild promoting effect on ethanol ingestion. Those rats that underwent IEA and BE, however, exhibited heightened and sustained ethanol self-administration (average of 2.12 g/kg/120 min, vs 1.15 g/kg/120 min of the other groups), that persisted throughout the BE sessions. IEA and a history of BE also promoted ethanol intake or preference in a two-bottle endpoint test.The study suggests that exposure to IEA exerts, when followed by BE at adulthood, promoting effects upon ethanol intake, particularly at concentrations ≥ 6%.

Maternal alcohol consumption during pregnancy may cause neurocognitive and behavioral disorders that can persist until adulthood. Epidemiological data has revealed an alarming increase in the frequency of alcohol intake in pregnant women. Nutritional variables may also have an impact on the behavioral alterations occasioned by alcohol during development. Moreover, omega-3, a polyunsaturated fatty acid necessary for normal brain development, is deficient in ethanol-treated animals. Although studies have shown that omega-3 supplementation after prenatal ethanol (EtOH) treatment improves some disorders, there are no reports about acute treatment with omega-3 in binge alcohol neurotoxic models during postnatal development. The goal of this study was to determine whether an administration of omega-3, after an acute ethanol dose in neonates, would be able to attenuate alcohol effects in offspring. Male/ female rats were administered ethanol (2.5 g/kg s.c. at 0 and 2 h) or saline on postnatal day (PND) 7, with a single dose of omega-3 (720 mg/kg) 15 min after the last alcohol injection. It was have found that EtOH-treated animals showed hyperlocomotion on PND 14 (pre-juvenile), and anxiety-like behavior was observed at all the three ages studied. Administration of omega-3 after EtOH treatment reduced hyperlocomotion and the anxiety-like behaviors on PND 14, but did not diminish the anxiety on either PND 20 or 30 (juvenile). In conclusion, acute ethanol exposure produced neurobehavioral alterations that persisted in the offspring, with omega-3 able to ameliorate these effects on PND 14. These data are relevant considering that omega-3 administration may have therapeutic effects through mitigating some of ethanol´s damaging consequences.

Binge drinking at adolescence is a risk factor for problematic alcohol (ethanol) consumption later in life, yet the murine studies that modelled this phenomenon via ethanol self-administration have provided mixed findings. Antagonism of the sigma-1 receptor (S1-R) system at adolescence modulates ethanol's motivational effects and intake. It is still unknown, however, whether this antagonism would protect against enhanced ethanol intake at adulthood after adolescent binge ethanol exposure.Exp. 1 and 2 tested adults male or female Wistar rats -exposed or not to ethanol self-administration at adolescence (postnatal days 31-49; nine 2-hour sessions of access to 8-10% ethanol)- for ethanol intake using 24-h two-bottle choice test (Exp. 1) or time restricted, single-bottle, tests (Exp. 2). Experiments 2-5 evaluated, in adolescent or adult rats, the effects of the S1-R antagonist S1RA on ethanol intake and on ethanol-induced conditioned taste or place aversion. Ancillary tests (e.g., novel object recognition, ethanol-induced locomotor activity) were also conducted.Adolescent ethanol exposure promoted ethanol consumption at both the restricted, single-bottle, and at the two-bottle choice tests conducted at adulthood. S1RA administration reduced ethanol intake at adulthood and facilitated the development of ethanol-induced taste (but not place) aversion.S1RA holds promise for lessening ethanol intake after chronic and substantial ethanol exposure in adolescence that results in heightened ethanol exposure at adulthood. This putative protective effect of S1-R antagonism may relate to S1RA exacerbating the aversive effects of this drug.

Background: The identification of factors promoting simultaneous alcohol and marijuana (SAM) use is important to promote early intervention efforts. The associations between impulsivity facets and SAM (or concurrent alcohol and marijuana, CAM) use have been analyzed in North American samples. These topics, however, remain unexplored in South American samples. This study assessed if internalizing symptoms, five impulsivity dimensions, and emotional regulation strategies differentiate between participants who reported last 2-month SAM use, CAM use, alcohol, or marijuana only use, or that reported no substance use. Methods: A sample of 1057 Argentinian citizens answered an online survey. A multinominal logistic regression was conducted on drug use membership. Results: Circa 25% of the sample reported SAM use. Higher sensation seeking differentiated between SAM use versus no substance use, and those with lower sensation seeking were more likely to be classified into the alcohol-only group or into the nonuse group, than into the SAM use group. Stress scores uniquely predicted membership into the alcohol-only category. Those with lower use of emotional suppression were more likely than nonusers to be classified in all drug use categories, except CAM use. Higher emotional suppression scores were associated with membership into the nonuse group or the alcohol-only group, when compared to the SAM use group. Hazardous drinking was significantly greater in SAM than in alcohol-only users. Conclusions: The study highlights the relevance of sensation seeking as a predictor of SAM use and pinpoints emotional suppression as common factor modulating hazardous drug use behaviors.

Ethanol-induced conditioned taste aversion (CTA) is greater in late adolescence or young adulthood than in early adolescence. The role of the sigma receptor system in this age-related difference has not been extensively explored, particularly in female rats. This study assessed the effects of the activation of sigma-1 receptors (S1-R), via the selective S1-R agonist PRE-084, on ethanol-induced CTA at early or at terminal adolescence/emerging adulthood (28 or 56 days-old at the beginning of the procedures, respectively) in female Wistar rats. The modulation of binge-like ethanol intake by PRE-084 was assessed at terminal adolescence. S1-R activation at the acquisition of ethanol-induced CTA attenuated such learning at terminal but not at early adolescence. PRE-084 did not significantly affect ethanol binge drinking in the terminal adolescents. These results highlight the role of S1-R in ethanol-induced CTA and suggest that differential functionality of this transmitter system may underlie age-specific sensitivities to the aversive effects of ethanol.

Early stress can increase vulnerability to psychopathological disorders, including substance use disorders. The effects of stress in the juvenile period of the rat, that extends between weaning and the onset of adolescence (equivalent to late human childhood), have received little attention. This study assessed short and long-term behavioral effects of juvenile stress, with a focus on effects on ethanol intake. Male and female Wistar rats were exposed to variable stress (restraint, elevated platform, forced swimming, and social instability) or to restraint stress only, between postnatal days 26 to 29 (PDs 26-29). During adolescence, patterns of anxiety (PD 31) and depression (PD 33), ethanol intake (PDs 36-45) and behavioral sensitivity to the effects of acute stress (PD 47) were evaluated. In adulthood, alcohol ingestion was assessed through two-bottle ethanol intake tests (PDs 75-85). An additional experiment measured blood ethanol levels after a limited access intake session in adolescence. Exposure to juvenile variable stress exerted very mild effects in adolescence, but reduced ethanol ingestion in adulthood, in females only. Ethanol intake during the limited access session was significantly correlated to blood alcohol levels. The results indicate that a schedule of juvenile variable stress that did not significantly alter anxiety-related behaviors induced, nonetheless, sexually dimorphic effects on ethanol intake in adulthood. Early stress exposure that reduced alcohol intake in Wistar rats has been associated with changes on brain opioid and dopamine receptors. These results highlight the impact of early stress exposure on adult female ethanol consumption and its possible underlying neurobiological changes, involving opioid and dopamine receptors.

AbstractPrenatal ethanol exposure (PEE) causes several neurobehavioral impairments in the fetus. Postnatal days (PDs) 4–9 in rodents are considered equivalent to the third trimester of gestation in humans. This period is characterized by high rates of synaptogenesis and myelination and the maturation of key structures and transmitter systems. Nutritional supplements, such as folate, have gained attention as putative treatments to mitigate detrimental effects of PEE. Folate is crucial for DNA synthesis and amino acid metabolism and heightens antioxidant defenses. The present study examined neurobehavioral effects of the concurrent administration of folate (20 mg/kg/day) and ethanol (5 g/kg/day) during PDs 4–9 in male and female Wistar rats. During PDs 16–18, the rat pups were tested for anxiety‐like and exploratory activity in the light–dark box (LDB), open field (OF), and concentric square field (CSF) tests. After weaning, they were tested for sucrose preference and ethanol intake. Neonatal ethanol exposure reduced body weight in infancy but did not enhance ethanol self‐administration or significantly affect performance in the OF or LDB. Neonatal ethanol exposure also reduced sucrose intake in the preference test and increased shelter‐seeking in the CSF, and folate significantly inhibited these effects. The present findings suggest that folate, a treatment that is devoid of serious side effects, can ameliorate some neurobehavioral effects of PEE.

Ethanol use during adolescence is a significant health problem, yet the pharmacological treatments to reduce adolescent binge drinking are scarce. The present study assessed, in male and female adolescent Wistar rats, if the sigma-1 receptor (S1-R) antagonists S1RA or BD-1063 disrupted ethanol drinking.Three times a week, for two weeks, the rats received the S1-R antagonists. Thirty min later they were exposed, for 2 h, to a bottle of 8% or 10 % v/v ethanol. A 24 h, two-bottle, ethanol intake test was conducted after termination of these procedures. A subset of these rats was tested for recognition memory via the novel object recognition test.The rats given 64 mg/kg S1RA drank, in each binge session, significantly less than vehicle counterparts. Male rats given 4 or 16 mg/kg S1RA drank significantly less than those given 0 mg/kg in session 3 or in session 1 and 2, respectively; whereas female rats given 4 or 16 mg/kg drank significantly less than females given 0 mg/kg in session 2-5 or in sessions 2-6, respectively. Administration of 32 mg/kg, but not of 2 or 8 mg/kg, BD-1063 suppressed, across sessions, ethanol drinking. S1-R antagonism reduced absolute ethanol drinking at the two-bottle choice post-test. Recognition memory was not affected by the ethanol exposure.The results indicate that S1-R antagonists may be promising targets to prevent increases in ethanol intake at adolescence. The persistent effect of S1-R antagonism in free-choice drinking suggests that modulation of the S1-R is altering plastic effects associated with ethanol exposure.