A new statistical model for binge drinking pattern classification in college-student populations

BackgroundBinge drinking (BD) among students is a frequent alcohol consumption pattern that produces adverse consequences. A widely discussed difficulty in the scientific community is defining and characterizing BD patterns. This study aimed to find homogenous drinking groups and then provide a new tool, based on a model that includes several key factors of BD, to assess the severity of BD regardless of the individual’s gender.MethodsUsing the learning sample (N1 = 1,271), a K-means clustering algorithm and a partial proportional odds model (PPOM) were used to isolate drinking and behavioral key factors, create homogenous groups of drinkers, and estimate the probability of belonging to these groups. Robustness of our findings were evaluated with Two validations samples (N2 = 2,310, N3 = 120) of French university students (aged 18–25 years) were anonymously investigated via demographic and alcohol consumption questionnaires (AUDIT, AUQ, Alcohol Purchase Task for behavioral economic indices).ResultsThe K-means revealed four homogeneous groups, based on drinking profiles: low-risk, hazardous, binge, and high-intensity BD. The PPOM generated the probability of each participant, self-identified as either male or female, to belong to one of these groups. Our results were confirmed in two validation samples, and we observed differences between the 4 drinking groups in terms of consumption consequences and behavioral economic demand indices.ConclusionOur model reveals a progressive severity in the drinking pattern and its consequences and may better characterize binge drinking among university student samples. This model provides a new tool for assessing the severity of binge drinking and illustrates that frequency of drinking behavior and particularly drunkenness are central features of a binge drinking model

Long Term Depression in Rat Hippocampus and the Effect of Ethanol during Fetal Life

Alcohol (ethanol) disturbs cognitive functions including learning and memory in humans, non-human primates, and laboratory animals such as rodents. As studied in animals, cellular mechanisms for learning and memory include bidirectional synaptic plasticity, long-term potentiation (LTP), and long-term depression (LTD), primarily in the hippocampus. Most of the research in the field of alcohol has analyzed the effects of ethanol on LTP; however, with recent advances in the understanding of the physiological role of LTD in learning and memory, some authors have examined the effects of ethanol exposure on this particular signal. In the present review, I will focus on hippocampal LTD recorded in rodents and the effects of fetal alcohol exposure on this signal. A synthesis of the findings indicates that prenatal ethanol exposure disturbs LTD concurrently with LTP in offspring and that both glutamatergic and γ-aminobutyric acid (GABA) neurotransmissions are altered and contribute to LTD disturbances. Although the ultimate mode of action of ethanol on these two transmitter systems is not yet clear, novel suggestions have recently appeared in the literature

GluN2B Subunit of the NMDA Receptor: The Keystone of the Effects of Alcohol During Neurodevelopment

International audienceThe glutamatergic system plays a central role in both the acute and chronic effects of ethanol. Among all the glutamate receptors the ionotropic NMDA receptors are crucial because of their role in synaptic plasticity. A large body of evidences suggests that short-term and long-term effects of ethanol may change synaptic plasticity via an alteration of the expression of the GluN2B subunit, one constitutive element of the NMDA receptor. The present review is focusing on the role of the GluN2B subunit after ethanol exposure during early life (in utero and adolescence) and also at adulthood. The roles of other NMDA subunits are also discussed in the context of the increasing evidence that the ratio of the different subunits, such as GluN2A-to-GluN2B, seems to better reflect the effects of ethanol and to explain how ethanol exposure can have short lasting and long lasting effects on synaptic plasticity, cognitive processes and some of the ethanol-related behaviors

Effects of serotonin and substance P on bulbar respiratory neurons in vivo

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Rhythmic activity from transverse brainstem slice of neonatal rat is modulated by nitric oxide.

We investigated the role of nitric oxide (NO) in the modulation of respiratory-like activity recorded from hypoglossal rootlets in brainstem slices of neonatal rats (P0-P8). Sodium nitroprusside (SNP), S-Nitroso-N-acetyl-D,L-penicillamine (SNAP) and diethylamine-NO (DEA-NO), three NO-donors, reversibly increased hypoglossal burst amplitude with inconsistent effects on burst frequency. Similar effects were also obtained with the endogenous substrate of nitric oxide synthase (NOS), L-arginine, whereas the inactive enantiomer D-arginine had no effect. The NO-trap agent methylene blue significantly depressed both the amplitude and frequency of hypoglossal activity while hemoglobin depressed only the amplitude. Furthermore, the addition of NO-trap agents significantly attenuated the excitatory response to SNP. Inhibiting NOS with either N(omega)-Nitro-L-Arginine (L-NNA) or 7-Nitroindazole (7-NI), decreased the amplitude of hypoglossal activity with no effects on frequency. Histochemical analysis of NADPH-diaphorase activity, a marker for NOS, was performed on slices not treated pharmacologically and in brainstem sections of newborn rats, perfused in situ. Comparison between in vitro and in vivo conditions indicated that NOS activity was maintained in slice preparations. Neurons in the ambiguus and hypoglossal nuclei (dorsal division) exhibited a granular staining, suggesting the presence of NADPHd-positive terminals. Neurons with cytoplasmic staining were identified in regions connected to the hypoglossal nucleus (nucleus tractus solitarius, paramedian and gigantocellular reticular nuclei). These neurons might be involved in nitrergic control of hypoglossal activity. Both pharmacological and histochemical data suggest that endogenous NO may reinforce the output activity of the medullary respiratory network

Biphasic effect of acamprosate on NMDA but not on GABAA receptors in spontaneous rhythmic activity from the isolated neonatal rat respiratory network.

International audienceAcamprosate (calcium acetylhomotaurinate) has been shown to be effective in attenuating relapse in human alcoholics. The precise mechanism for acamprosate has been yet to be determined as there may be multiple sites of action for this drug. We investigated the mechanism of action of acamprosate on a spontaneous rhythmic activity recorded from hypoglossal nerve rootlet (XII) in neonatal rat brainstem slices. At 30 microM, acamprosate reversibly increased burst amplitude and reduced burst frequency, whereas at higher concentrations (100-400 microM) it induced a reversible and concentration-dependent inhibition of this activity. Interestingly, acamprosate (30 microM) enhanced the effects of low NMDA-induced excitation (1.5 microM), but inhibited higher NMDA-induced excitation (2.5, 5 microM) by 50-70%, demonstrating a differential effect on NMDA-induced excitation. Blockade of GABAA receptors did not affect the increase in amplitude of 30 microM acamprosate and partially abolished the inhibitory effects of 200 microM acamprosate. At 200 microM, acamprosate reduced high NMDA-induced excitation and abolished NMDA-evoked excitatory tonic phase, suggesting that excitatory effect of low concentrations of acamprosate mainly involved NMDA receptors, while the inhibitory effects at higher concentration included an increase in GABAA-mediated inhibition with a reduction of NMDA-mediated excitation. Consequently, combined blockade of both receptors abolished all effects of acamprosate tested at all concentrations. These results show that the effects of acamprosate are mediated via both GABAA and NMDA receptors and suggest a partial co-agonist role on NMDA receptors, at the level of a spontaneously active network

Sex difference in the vulnerability to hippocampus plasticity impairment after binge-like ethanol exposure in adolescent rat: Is estrogen the key?

International audienceBinge drinking during adolescence induces memory impairments, and evidences suggest that females are more vulnerable than males. However, the reason for such a difference is unclear, whereas preclinical studies addressing this question are lacking. Here we tested the hypothesis that endogenous estrogen level (E2) may explain sex differences in the effects of ethanol on hippocampus plasticity, the cellular mechanism of memory. Long-term depression (LTD) in hippocampus slice of pubertal female rats was recorded 24 h after two ethanol binges (3 g/kg, i.p., 9 h apart). Neither the estrous cycle nor ethanol altered LTD. However, if ethanol was administered during proestrus (i.e., at endogenous E2 peak), LTD was abolished 24 h later, whereas NMDA-fEPSPs response to a GluN2B antagonist increased. The abolition of LTD was not observed in adult female rats. Exogenous E2 combined with ethanol replicated LTD abolition in pubertal, prepubertal female, and in pubertal male rats without changes in ethanol metabolism. In male rats, a higher dose of ethanol was required to abolish LTD at 24-h delay. In pubertal female rats, tamoxifen, an antagonist of estrogen receptors, blocked the impairing effects of endogenous and exogenous E2 on LTD, suggesting estrogen interacts with ethanol through changes in gene expression. In addition, tamoxifen prevented LTD abolition at 24 h but not at 48-h delay. In conclusion, estrogen may explain the increased vulnerability to ethanol-induced plasticity impairment seen in females compared with males. This increased vulnerability of female rats is likely due to changes in the GluN2B subunit that represent a common target between ethanol and estrogen