Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats

Obernier, Jennifer; White, Aaron M.; Swartzwelder, H. Scott; Crews, Fulton T.

doi:10.1016/s0091-3057(02)00715-3

Cited by 235 publications

(238 citation statements)

References 51 publications

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“…There is much experimental evidence indicating that binge ethanol administration produces blood alcohol levels similar to or lower than those obtained in the current study causing observable neuronal cell loss and that this effect is especially prominent in the hippocampus, entorhinal and frontal cortex (Collins et al 1996;Obernier et al 2002b;Zharkovsky et al 2003;Hamelink et al 2005). Neuronal damage was visualized and quantified in the form of argyrophilic neurons with cupric-silver staining techniques (Collins et al 1996;Hamelink et al 2005), which, although methods of choice to assess irreversible neurodegeneration caused by a great variety of insults, have the disadvantage that they do not identify the nature of the damaged neuron.…”

Section: Discussionsupporting

confidence: 62%

Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain

et al. 2006

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Rationale Ecstasy abuse commonly occurs in hot, overcrowded environments in combination with alcohol. Around 90% of ecstasy users take ethanol; over 70% of these users also often drink alcohol at hazardous levels. Objectives We wished to examine whether binge ethanol administration enhanced the long-lasting 5-HT neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats maintained at high ambient temperature and the role of acetaldehyde. Materials and methods Rats were treated with a 4-day ethanol regimen leading to plasma ethanol levels of around 450 mg/dl. On day 5, rats were placed at 30°C and administered MDMA (5 mg/kg). Rectal temperature and hydroxyl radical formation were measured immediately before and up to 6 h after MDMA. 5-HT concentration and 5-HT transporter density were determined 7 days later. A group of rats received cyanamide (50 mg/kg) on days 1 and 3 of the 4-day-ethanol inhalation. Results In ethanol treated rats, MDMA produced a hyperthermic response similar to that observed in controls but enhanced the loss of 5-HT concentration and 5-HT transporter density in the hippocampus. Cyanamide elevated the plasma acetaldehyde concentration fivefold to sevenfold, reduced the MDMA-induced hyperthermia and increased the neuronal damage with neurotoxicity also appearing in the cortex. MDMA increased hydroxyl radical production in the hippocampus, the effect being more marked in rats pre-exposed to ethanol.Conclusions Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity by a mechanism not related to changes in acute hyperthermia but probably involving hydroxyl radical formation. The magnitude of this effect is more pronounced after increasing plasma acetaldehyde levels by aldehyde dehydrogenase inhibition.

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Section: Discussionsupporting

confidence: 62%

Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain

et al. 2006

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“…116 For example, chronic intermittent ethanol exposure is the rat analog of human binge drinking. Chronic intermittent ethanol exposure was associated with reduced neurogenesis in the rat hippocampus 117 and long-term alteration of serotonergic function, 118 likely resulting in permanently altered forebrain functioning. Therefore, adolescent vulnerability to the neurotoxic effects of alcohol may be exacerbated by the typical pattern of adolescent drinking, which often involves intermittent bouts of heavy drinking (ie, periodic binge drinking).…”

Section: Alcohol and The Developing Adolescent Brainmentioning

confidence: 99%

A Developmental Perspective on Alcohol and Youths 16 to 20 Years of Age

Brown¹,

McGue²,

et al. 2008

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Late adolescence (ie, 16 -20 years of age) is a period characterized by escalation of drinking and alcohol use problems for many and by the onset of an alcohol use disorder for some. This heightened period of vulnerability is a joint consequence of the continuity of risk from earlier developmental stages and the unique neurologic, cognitive, and social changes that occur in late adolescence. We review the normative neurologic, cognitive, and social changes that typically occur in late adolescence, and we discuss the evidence for the impact of these transitions on individual drinking trajectories. We also describe evidence linking alcohol abuse in late adolescence with neurologic damage and social impairments, and we discuss whether these are the bases for the association of adolescent drinking with increased risks of mental health, substance abuse, and social problems in adulthood. Finally, we discuss both the challenges and successes in the treatment and prevention of adolescent drinking problems. I N THE UNITED States, alcohol involvement sometimes starts but more often escalates between 16 and 20 years of age, when youths are also experiencing dramatic physical, emotional, and social changes. Specifically, a variety of forms of hazardous drinking emerge during middle to late adolescence and, for many youths, these problematic patterns of drinking continue to escalate through 18 to 20 years of age, the period of greatest risk for the onset of an alcohol use disorder (AUD).In seeking to understand youth development and alcohol involvement, it is important to consider all dimensions of functioning, because the interrelated cognitive, biological, social, and affective changes that occur during adolescence not only affect each another but also influence an individual's risk of problem drinking. In particular, the timing, sequence, and synchrony of developmentally specific transitions can affect how well youths master new roles, as well as continuities and discontinuities in their behavior. Therefore, developmental models representing a range of theoretical orientations, including systems theory, behavioral genetics, and developmental psychopathology, hold great promise for advancing our understanding of the processes that underlie adolescent changes, including the emergence of alcohol use and abuse.The need for developmental approaches is underscored by the existence of a consistent body of research showing that the escalation in drinking and the emergence of AUDs in middle and late adolescence have behavioral, social, and biological roots from earlier developmental stages. Moreover, it is becoming increasingly clear that alcohol involvement in adolescence has both short-and long-term effects on health and well-being at later developmental stages. Importantly, the consequences of adolescent drinking seem to differ from those associated with adult drinking, because there is increasing evidence that adolescents are especially vulnerable to the adverse effects of heavy alcohol use on both biological and socia...

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“…Of particular interest in the study of cognitive impairments resulting from repeated periods of alcohol exposure and withdrawal are connections to the prefrontal cortex and hippocampus. Although there is good evidence that repeated intermittent ethanol administration, or repeated withdrawal, results in both physiological (Stephens et al 2005) and pathological (Obernier et al 2002a,b) changes in hippocampus, the limited evidence available has so far failed to demonstrate a marked impairment in behaviours, such as spatial learning (Borlikova et al 2006a;Obernier et al 2002b), or contextual conditioning (Borlikova et al 2006a), thought to be mediated by hippocampal processes. Borlikova et al (2006b), however, did find a marked impairment in a negative patterning task (Bussey et al 2000), in which rats were required to initiate a response when either a light or a tone stimulus was presented, but to inhibit the response when both stimuli were presented simultaneously.…”

Section: Effects Of Ethanol Withdrawal On Frontal Cortical Function Imentioning

confidence: 99%

Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex

Stephens

Duka

2008

Phil. Trans. R. Soc. B

173

142

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Binge drinking is an increasingly recognized problem within the UK. We have studied the relationship of binge drinking to cognitive and emotional functioning in young adults, and have found evidence for increased impulsivity, impairments in spatial working memory and impaired emotional learning. Since in human studies it is difficult to understand whether such behavioural changes predate or are a consequence of binge drinking, we have also studied parallel behaviours in a rodent model, in which rats are exposed to intermittent episodes of alcohol consumption and withdrawal. In this model, and in parallel with our findings in human binge drinkers, and alcoholic patients who have undergone multiple episodes of detoxification, we have found evidence for impairments in aversive conditioning as well as increased impulsivity. These behavioural changes are accompanied by facilitated excitatory neurotransmission and reduced plasticity (long-term potentiation (LTP)) in amygdala and hippocampus. The impaired LTP is accompanied by both impaired associative learning and inappropriate generalization of previously learned associations to irrelevant stimuli. We propose that repeated episodes of withdrawal from alcohol induce aberrant neuronal plasticity that results in altered cognitive and emotional competences.

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Cognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats

Cited by 235 publications

References 51 publications

Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain

Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity in rat brain

A Developmental Perspective on Alcohol and Youths 16 to 20 Years of Age

Cognitive and emotional consequences of binge drinking: role of amygdala and prefrontal cortex

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