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Effects of nicotine, administered by continuous infusion via osmotic minipumps, were studied on the operant self-administration of alcohol by rats, using a variable interval (15 s) schedule, and measuring the acquisition, maintenance, extinction and reinstatement of responding for alcohol. Doses of nicotine of 0.25, 1.25 and 7.5 mg/kg/24 h had no significant effects on the maintenance of responding for alcohol, but 5 mg/kg/24 h nicotine resulted in a significant increase in responding on the lever delivering the reward when water was substituted for the alcohol, indicating delayed extinction of responding. During infusion of 2.5 mg/kg/24 h nicotine, responding was significantly greater over the "sucrose-fading" training sessions, during acquisition of responding, when mixtures of alcohol and sucrose were provided as reward. When minipumps infusing 2.5 mg/kg/24 h nicotine were implanted after the alcohol responding had been acquired, the responding for alcohol increase during the first week of nicotine infusion, but corresponding nicotine infusion doses of 0.25, 1.25 and 7.5 had no significant effects. The results indicate that nicotine can increase operant responding for alcohol and this is crucially dependent on the dose of nicotine and the time of testing. The results have implications for the frequently encountered dependence on the combination of alcohol and nicotine.

The identification of the neurobiological concomitants of ethanol dependence and withdrawal would not only provide a better understanding of the basic nature of such phenomena, but would also facilitate the development of techniques of detection, prevention, and treatment of alcoholic disease and its psychobiological consequences.

Chronic exposure to ethanol can cause deficits in learning and memory. It has been suggested that withdrawal is potentially more damaging than the ethanol exposure per se. Therefore, we explored the effect of repeated episodic exposure to ethanol on key regulators of cortical activity, the neurotrophins. Rats were exposed to ethanol via a liquid diet for 3 days per week for 6-24 weeks. Control rats were pair-fed an isocaloric liquid diet or ad libitum fed chow and water. The concentrations of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined using enzyme-linked immunosorbant assays (ELISAs). Five telencephalic structures were examined: parietal cortex, entorhinal cortex, hippocampus, the basal nucleus, and the septal nuclei. All five areas expressed each of the three neurotrophins; BDNF was most abundant and NGF the least. The parietal cortex was susceptible to ethanol exposure, NGF and BDNF content increased, and NT-3 content fell, whereas no changes were detectable in the entorhinal cortex. In the hippocampus, the amount all three neurotrophins increased following episodic ethanol exposure. Neurotrophin content in the two segments of the basal forebrain was affected; NGF and NT-3 content in the basal forebrain was reduced and NGF and BDNF content in the septal nuclei was increased by ethanol exposure. In many cases where ethanol had an effect, the change was transient so that by 24 weeks of episodic exposure, no significant changes were evident. Thus, the effects of ethanol are site- and time-dependent. This pattern differs from changes caused by chronic ethanol exposure, hence, neurotrophins must be vulnerable to the effects of withdrawal. Furthermore, the ethanol-induced changes do not appear to fit a model consistent with retrograde regulation, rather they suggest that neurotrophins act through autocrine/paracrine systems.

In rodents, chronic intermittent ethanol vapor exposure (CIE) produces alcohol dependence, alters the activity of pyramidal neurons and decreases the number of glial progenitors in the medial prefrontal cortex (mPFC). Adult male Wistar rats were exposed to CIE and were injected with mitotic markers to label and phenotype proliferating cells to test the hypothesis that CIE produces concurrent alterations in the structure of pyramidal neurons and the cell cycle kinetics and developmental stages of glial progenitors in the mPFC. Medial prefrontal cortical tissue was processed for Golgi-Cox staining, immunohistochemistry and Western blotting analysis. CIE increased dendritic arborization and spine densities within basal and apical dendrites of pyramidal neurons via aberrant reorganization of actin cytoskeleton-associated molecules. CIE concomitantly increased the expression of total NR2B subunits without affecting phosphorylation of NR2B at Tyr-1472 or levels of PSD-95. CIE reduced the length of S-phase of the cell cycle of glial progenitors and reduced proliferation and differentiation of progenitors into bHLH transcription factor Olig2-expressing premyelinating oligodendrocyte progenitor cells (OPCs). CIE also produced a corresponding hyperphosphorylation of Olig2, and reduced expression of myelin basic protein. Our findings demonstrate that CIE-induced alterations in OPCs and myelin-related proteins are associated with profound alterations in the structure of pyramidal neurons. In sum, our results not only provide evidence that alcohol dependence leads to pathological changes in the mPFC, which may in part define a cellular basis for cognitive impairments associated with alcoholism, but also show dependence-associated morphological changes in the PFC at the single neuron level.

Background and ObjectivesThe study examined the effects of an alcohol challenge on naturalistic drinking among alcohol‐dependent individuals and explored brief motivational interviewing (MI) as a potential intervention for these participants.MethodAlcohol‐dependent individuals (n = 32, eight females) completed the intake assessment, alcohol challenge, one MI session, and 1‐month follow‐up (87.5% retention) where they completed measures of drinking and motivation for change.ResultsAs expected, multilevel mixed models revealed that drinking did not increase post‐alcohol challenge. Participants reported a reduction in ambivalence, drinking days, and a trend towards fewer total drinks between the MI and 1‐month follow‐up.ConclusionsConsistent with other studies, the alcohol challenge did not worsen alcohol use. Results support further investigation of brief MI for alcohol‐dependent participants in alcohol challenges.Scientific SignificanceAlcohol administration to alcohol‐dependent participants appears to not exacerbate naturalistic drinking. MI may be a feasible intervention for non‐treatment seeking alcohol‐dependent participants in alcohol challenge studies. (Am J Addict 2014;23:96–101)

Pages vi-xi are misnumbered as pages iv-ix. ; Alcohol is one of the most widely used psychoactive substance in the world, yet there are conflicting findings related to its long-term effect on cognition. Some research has identified a U-shaped relationship between alcohol consumption and cognition, while negative relationships have been identified in other studies. Methodological issues, particularly the time at which alcohol consumption was measured relative to when cognition was measured, wide variability in definitions of "moderate" alcohol consumption, and selecting appropriate comparison groups, have made exploring the effects of alcohol on cognition during aging difficult. The current study examined the relationship between drinking at three separate time points (between the ages of 50 and 74) and cognition in older adulthood. Results revealed that the quantity of self-reported drinks over the three time points was a significant predictor of cognition in older adulthood (b=0.001; p0.05). Overall, the results suggest no that there is not a meaningful relationship between alcohol consumption and cognitive functioning in older adulthood in this sample. There were few consistent heavy drinkers (n=71), but a large number of consistent moderate drinkers (n=1,847), although even the moderate drinkers did not consume much alcohol (mean alcohol consumption = 15.3 drinks/month; median alcohol consumption = 5.0 drinks/month). This may have limited the ability to detect clinically meaningful differences. Future studies should rely on more standardized alcohol measures, large, diverse samples, and inclusion of cognitive measures assessing visuospatial abilities and executive functioning, in order to better ...

Recent theories of the effects of ethanol on the brain have focused on its direct actions on neuronal membrane proteins. However, neuromolecular mechanisms whereby ethanol produces its CNS effects in low doses typically used by social drinkers (e.g., 2–3 drinks, 10–25 mm, 0.05–0.125 gm/dl) remain less well understood. We propose the hypothesis that ethanol may act by introducing a level of randomness or “noise” in brain electrical activity. We investigated the hypothesis by applying a battery of tests originally developed for nonlinear time series analysis and chaos theory to EEG data collected from 32 men who had participated in an ethanol/placebo challenge protocol. Because nonlinearity is a prerequisite for chaos and because we can detect nonlinearity more reliably than chaos, we concentrated on a series of measures that quantitated different aspects of nonlinearity. For each of these measures the method of surrogate data was used to assess the significance of evidence for nonlinear structure. Significant nonlinear structure was found in the EEG as evidenced by the measures of time asymmetry, determinism, and redundancy. In addition, the evidence for nonlinear structure in the placebo condition was found to be significantly greater than that for ethanol. Nonlinear measures, but not spectral measures, were found to correlate with a subject’s overall feeling of intoxication. These findings are consistent with the notion that ethanol may act by introducing a level of randomness in neuronal processing as assessed by EEG nonlinear structure.

Prenatal alcohol exposure is known to cause damage to the central nervous system. This study sought to further elucidate the structural brain damage that occurs following prenatal alcohol exposure in both children and rats. Two children with histories of maternal alcohol abuse but who did not qualify for a diagnosis of Fetal Alcohol Syndrome (FAS), based on established criteria, underwent magnetic resonance imaging. Reduced volumes were found for the cerebrum and cerebellum. In addition, the proportional volume of the basal ganglia was reduced, although the proportional volumes of cortical and subcortical fluid, cortical gray matter, limbic and nonlimbic cortex, and diencephalic structures were unaffected. These findings are compared with our recent MRI findings in two cases of FAS. In addition, the caudate-putamen and ventricular areas were assessed in rats exposed to alcohol prenatally. Whereas the overall brain section area was not reduced in size, the area of the caudate-putamen was reduced and that of the ventricles was enlarged.

BACKGROUND: On the subject of cerebral infarction, it is a common saying that “time is brain”. The prognosis of a patient who has received thrombolysis after such an infarction becomes significantly better as the time from symptom debut until the thrombolytic bolus lessens. Identifying the factors that contribute to longer times before thrombolysis for patients could thus be meaningful, and this is exactly what the aim of this assignment is. METHODS: Data was collected from the digital documents of patients who had received thrombolytic treatment from Akershus University Hospital. Both linear and categorical variables were registered from fields such as the patients’ background, vitals and disease severity. Time from onset to arrival at the hospital and time from arrival to the start of the infusion were registered in detail, and potentially delaying factors such as uncertain time of symptom debut and suspected contraindications were explored. The official Norwegian limit for delayed thrombolysis is 40 minutes, and thus this was chosen as the limit in this assignment as well. RESULTS: A total of 100 patients were registered, having received thrombolysis in 2015 and 2016. 50 men and 50 women were registered, with a mean age of 67.6. The mean NIHSS on arrival was 7.63 (standard variance 6.06). The mean time from symptom debut until arrival was 90.09 min (standard variance 48.91) and the mean time from arrival until the thrombolysis was given was 46.24 min (standard variance 33.40). 48.0% of the patients received thrombolysis more than 40 min after arrival, thus defining it as delayed treatment. The factors which showed a significant association with delayed treatment, using a confidence interval of 95%, were smoking (p=0.028), necessary prethrombolytic reduction in blood pressure (p=0.002), suspected contraindication (p=0.023) and uncertain severity of disease (p=0.001). Factors that unexpectedly showed no significant association with delayed treatment were uncertain time of symptom debut and high NIHSS on arrival. CONCLUSION: Factors that may have contributed to delayed thrombolysis were smoking, prethrombolytic reduction of blood pressure, suspected contraindications and uncertain severity of disease. In order to shorten the time from arrival to treatment, the effects of these factors on the efficiency of the thrombolytic procedure must be minimized. This could be attempted by using tools such as stricter, clearer guidelines and hospital campaigns targeting the attitudes of the personnel. All this being said, this assignment has made it clear that the treatment of cerebral infarctions is largely successful.