Long-Term Potentiation in the Rat Hippocampus Is Reversibly Depressed by Chronic Intermittent Ethanol Exposure

Roberto, Marisa; Nelson, Thomas E.; Ur, C. L.; Gruol, Donna L.

doi:10.1152/jn.2002.87.5.2385

Cited by 94 publications

(81 citation statements)

References 58 publications

(64 reference statements)

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“…Binge ethanol exposure also results in necrotic cell death and neurodegeneration in the hippocampus (Obernier et al 2002;Hamelink et al 2005). Moreover, evidence from studies examining the effects of ethanol on hippocampal plasticity suggests that chronic ethanol inhibits hippocampal LTP (Durand and Carlen 1984;Tremwel and Hunter 1994;Roberto et al 2002Roberto et al , 2003, which may underlie chronic ethanol-induced deficits in hippocampus-dependent learning and memory. Ethanol inhibition of LTP may result from decreased excitability of hippocampal neurons due to blockage of NMDA receptors, specifically NR1/ NR2A or NR1/NR2B subtypes (Hoffman et al 1989;Lovinger et al 1989;Schummers and Browning 2001;Izumi et al 2005; for review, see Allgaier 2002) as well as activation of inhibitory GABA A receptors (Allan and Harris 1986;Aguayo 1990;Reynolds et al 1992;Schummers and Browning 2001).…”

Section: Effects Of Prolonged Alcohol Exposure On Hippocampal Functionmentioning

confidence: 99%

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

2016

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It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawalinduced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates.Addiction is a major worldwide health problem that results in maladaptive behavioral changes, some that can last a lifetime. This behavioral plasticity, often times maladaptive, must be associated changes in neural plasticity. In fact, it has been noted multiple times that there is a high degree of overlap between the neurobiology of learning and memory and the neurobiology of addiction

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Section: Effects Of Prolonged Alcohol Exposure On Hippocampal Functionmentioning

confidence: 99%

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

2016

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“…Chronic alcohol treatment is also associated with longlasting changes in synaptic plasticity and learning and memory deficits. Thus, the hippocampus may be important for some shared cognitive features of addiction, depression, and schizophrenia (Walker and Freund 1971;Santin et al 2000;Roberto et al 2002).…”

Section: Drug Abuse and Addictionmentioning

confidence: 99%

Adult Neurogenesis and Psychiatric Disorders

Kang

Wen

Song

et al. 2016

Cold Spring Harb Perspect Biol

152

118

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Psychiatric disorders continue to be among the most challenging disorders to diagnose and treat because there is no single genetic or anatomical locus that is causative for the disease. Current treatments are often blunt tools used to ameliorate the most severe symptoms, at the risk of disrupting functional neural systems. There is a critical need to develop new therapeutic strategies that can target circumscribed functional or anatomical domains of pathology. Adult hippocampal neurogenesis may be one such domain. Here, we review the evidence suggesting that adult hippocampal neurogenesis plays a role in emotional regulation and forms of learning and memory that include temporal and spatial memory encoding and context discrimination, and that its dysregulation is associated with psychiatric disorders, such as affective disorders, schizophrenia, and drug addiction. Further, adult neurogenesis has proven to be an effective model to investigate basic processes of neuronal development and converging evidence suggests that aberrant neural development may be an etiological factor, even in late-onset diseases. Constitutive neurogenesis in the hippocampus of the mature brain reflects large-scale plasticity unique to this region and could be a potential hub for modulation of a subset of cognitive and affective behaviors that are affected by multiple psychiatric disorders.

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“…Chronic ethanol treatment significantly impairs hippocampal long-term potentiation (13) and produces progressive learning and memory deficits across a variety of behavioral tests, including active avoidance (14) and spatial memory (15). The LieberDeCarli ethanol diet reliably reproduces many of the effects of alcoholism observed in humans, including liver changes, gastrointestinal effects, and peripheral neuropathies (16).…”

mentioning

confidence: 99%

Selective impairment of hippocampal neurogenesis by chronic alcoholism: Protective effects of an antioxidant

Herrera

Yagüe²,

Johnsen-Soriano³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

242

159

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A major pathogenic mechanism of chronic alcoholism involves oxidative burden to liver and other cell types. We show that adult neurogenesis within the dentate gyrus of the hippocampus is selectively impaired in a rat model of alcoholism, and that it can be completely prevented by the antioxidant ebselen. Rats fed for 6 weeks with a liquid diet containing moderate doses of ethanol had a 66.3% decrease in the number of new neurons and a 227-279% increase in cell death in the dentate gyrus as compared with paired controls. Neurogenesis within the olfactory bulb was not affected by alcohol. Our studies indicate that alcohol abuse, even for a short duration, results in the death of newly formed neurons within the adult brain and that the underlying mechanism is related to oxidative or nitrosative stress. Moreover, these findings suggest that the impaired neurogenesis may be a mechanism mediating cognitive deficits observed in alcoholism.A lcohol dependence and abuse are among the most prevalent mental disorders in the United States, with Ϸ14% of the general population meeting criteria for alcohol dependence at some time in their lives and 7% having been dependent in the past year (1). Severe cognitive impairment consistently occurs in chronic alcoholism regardless of the presence of associated thiamine deficits (Korsakoff syndrome), and it includes progressive and severe anterograde learning deficits, implicating impairment in hippocampal circuits. However, no consistent pathological finding has yet been identified. The neuropathological correlate of the cognitive impairments accompanying alcoholism remains unclear (2-4). In animal models of alcoholism, a thinning of the granular layer of the dentate gyrus (DG) is attributed to neuronal loss (5). These findings, however, have been difficult to confirm in human brains (6) and have been contested in animal models as well (7). Human postmortem studies account for the duration of alcohol abuse but not the duration of abstinence before death. Interestingly, MRI studies demonstrate reduction of hippocampal volumes in alcoholics that are reversible after short periods of abstinence (8). The loss of hippocampal volume has been attributed to changes in white matter (6), but the incorporation of newly formed neurons to the DG could also be affected by alcohol. Similarly, hippocampaldependent cognitive functions have also shown reversibility after comparable periods of abstinence.Neurogenesis is primarily a developmental process that involves the proliferation, migration, and differentiation into neurons of primordial CNS stem cells (9, 10). Neurogenesis declines until it ceases in the young adult mammalian brain with two exceptions: the olfactory bulb (OB) and the hippocampus produce new neurons throughout adult life. In the subgranular cell layer of the DG, hippocampal progenitors proliferate and migrate a short distance into the granule cell layer, where they differentiate into hippocampal granule cells. Although multiple factors seem to regulate adult neurogenesis including...

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Long-Term Potentiation in the Rat Hippocampus Is Reversibly Depressed by Chronic Intermittent Ethanol Exposure

Cited by 94 publications

References 58 publications

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

Adult Neurogenesis and Psychiatric Disorders

Selective impairment of hippocampal neurogenesis by chronic alcoholism: Protective effects of an antioxidant

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