Alcohol dependence is characterized by a reduction in reward threshold, development of a negative affective state, and significant cognitive impairments. Dependence-induced glutamatergic ...neuroadaptations in the neurocircuitry mediating reward, affect and cognitive function are thought to underlie the neural mechanism for these alterations. These changes serve to promote increased craving for alcohol and facilitate the development of maladaptive behaviors that promote relapse to alcohol drinking during periods of abstinence.
To review the extant literature on the effects of chronic alcohol exposure on glutamatergic neurotransmission and its impact on reward, affect and cognition.
Evidence from a diverse set of studies demonstrates significant enhancement of glutamatergic activity following chronic alcohol exposure. In particular, up-regulation of GluN2B-containing NMDA receptor expression and function is a commonly observed phenomenon that likely reflects activity-dependent adaptive homeostatic plasticity. However, this observation as well as other glutamatergic neuroadaptations are often circuit and cell-type specific.
Dependence-induced alterations in glutamate signaling contribute to many of the symptoms experienced in addicted individuals and can persist well into abstinence. This suggests that they play an important role in the development of behaviors that increase the probability for relapse. As our understanding of the complexity of the neurocircuitry involved in the addictive process has advanced, it has become increasingly clear that investigations of cell-type and circuit-specific effects are required to gain a more comprehensive understanding of the glutamatergic adaptations and their functional consequences in alcohol addiction.
While pharmacological treatments for alcohol dependence and relapse targeting the glutamatergic system have shown great promise in preclinical models, more research is needed to uncover novel, possibly circuit-specific, therapeutic targets that exhibit improved efficacy and reduced side effects.
•Alcohol dependence is associated with alterations in glutamatergic neuroplasticity.•Alterations in NMDA receptor mediated activity are common across brain regions.•Dependence-induced changes occur in regions mediating reward, affect and cognition.•Circuit-specific changes may present new targets for the treatment of alcoholism.
A recent increase in the amount of dissolved reactive phosphorus (DRP) entering the western Lake Erie basin is likely due to increased spring storm events in combination with issues related to ...fertilizer application and timing. These factors in combination with warmer lake temperatures have amplified the spread of toxic algal blooms. We assessed the attitudes of farmers in northwest Ohio toward taking at least one additional action to reduce nutrient loss on their farm. Specifically, we (1) identified to what extent farm and farmer characteristics (e.g., age, gross farm sales) as well as risk‐based beliefs (e.g., efficacy, risk perception) influenced attitudes, and (2) assessed how these characteristics and beliefs differ in their predictive ability based on unobservable latent classes of farmers. Risk perception, or a belief that negative impacts to profit and water quality from nutrient loss were likely, was the most consistent predictor of farmer attitudes. Response efficacy, or a belief that taking action on one's farm made a difference, was found to significantly influence attitudes, although this belief was particularly salient for the minority class of farmers who were older and more motivated by profit. Communication efforts should focus on the negative impacts of nutrient loss to both the farm (i.e., profit) and the natural environment (i.e., water quality) to raise individual perceived risk among the majority, while the minority need higher perceived efficacy or more specific information about the economic effectiveness of particular recommended practices.
Key Points
Farmers' attitudes are largely driven by perceived risk and response efficacy
The majority of farmers (∼93%) have a positive attitude toward taking action
Younger farmers already engaged in conservation have a more positive attitude
Dopamine (DA) receptors in the medial prefrontal cortex (mPFC) exert powerful effects on cognition by modulating the balance between excitatory and inhibitory neurotransmission. The present study ...examined the impact of chronic intermittent ethanol (CIE) exposure on cognitive function and DA receptor-mediated neurotransmission in the rat mPFC. Consistent with alterations in executive function in alcoholics, CIE-exposed rats exhibited deficits in behavioral flexibility in an operant set-shifting task. Since alterations in dopaminergic neurotransmission in the mPFC have been implicated in a number of behavioral disorders including addiction, studies were then performed in the adult acute slice preparation to examine changes in DA receptor function in the mPFC following CIE exposure. In slices obtained from control rats, DA receptor stimulation was observed to exert complex actions on neuronal firing and synaptic neurotransmission that were not only dependent upon the particular receptor subtype but also whether it was a pyramidal cell or a fast-spiking interneuron. In contrast to slices from control rats, there was a near complete loss of the modulatory actions of D2/D4 receptors on cell firing and neurotransmission in slices obtained immediately, 1 and 4 weeks after the last day of CIE exposure. This loss did not appear to be associated with changes in receptor expression. In contrast, CIE exposure did not alter D1 receptor function or mGluR1 modulation of firing. These studies are consistent with the suggestion that chronic alcohol exposure disrupts cognitive function at least in part through disruption of D2 and D4 receptor signaling in mPFC.
Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, ...the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28-42 on γ-aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch-clamp electrophysiology in acute slices obtained at different postnatal ages revealed a developmental increase in the GABA
receptor-mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE-exposed rats, the amplitude of the tonic current was significantly reduced compared with controls when tested at postnatal days 45, 60 and 90-120. This AIE-induced reduction in tonic current was found to reflect attenuation of currents mediated by δ-subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE-exposed adult rats compared with control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by δ-GABA
receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of δ-GABA
subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in δ-GABA
tonic currents in the adult prelimbic cortex that may contribute to deficits in decision-making and behavioral control in adulthood.
Delayed maturation of the adolescent prefrontal cortex may render it particularly vulnerable to insults, including those associated with drugs of abuse. Using a rat model of binge alcohol exposure, ...the present study examined the effect of adolescent intermittent ethanol (AIE) exposure during postnatal days 28–42 on γ‐aminobutyric acid (GABA)ergic neurotransmission in the prelimbic cortex. In control rats, patch‐clamp electrophysiology in acute slices obtained at different postnatal ages revealed a developmental increase in the GABAA receptor‐mediated tonic current in layer V pyramidal neurons but no change in layers II/III when measured in the adult. In slices from AIE‐exposed rats, the amplitude of the tonic current was significantly reduced compared with controls when tested at postnatal days 45, 60 and 90–120. This AIE‐induced reduction in tonic current was found to reflect attenuation of currents mediated by δ‐subunit containing receptors. Consistent with this, facilitation of the tonic current by bath application of either ethanol or allopregnanolone was attenuated in slices from AIE‐exposed adult rats compared with control rats. However, expression of this facilitation as a percent of the amplitude of the total current mediated by δ‐GABAA receptors revealed that AIE did not alter their sensitivity to either agonist. Lastly, immunohistochemistry and Western blot analysis revealed no change in the expression of δ‐GABAA subunits or their surface expression. Taken together, these studies reveal that AIE exposure results in persistent deficits in δ‐GABAA tonic currents in the adult prelimbic cortex that may contribute to deficits in decision‐making and behavioral control in adulthood.
The adolescent prefrontal cortex (PFC) is particularly vulnerable to developmental insults from alcohol abuse. Using a rat model of adolescent alcohol exposure, the present study examined the effect of adolescent alcohol exposure on GABAergic neurotransmission in the adult PFC. We show that adult rats exposed to alcohol during adolescence exhibit prolonged deficits in tonic GABAergic currents. These observations may contribute to deficits in decision‐making and behavioral control in adulthood.
Our artists' book, Field Notes, explores the idea of sequence and mapping. Our collaboration uses mapping as a practical activity for articulating three fields in Devon, involving different stages of ...drawing, writing and performing. Elizabeth-Jane Burnett, a writer, is interested in whether the fields hold memories and how these might be accessed through historical research, engagement with organisms in the fields today, and performative processes. Rebecca Thomas, a visual artist, explores making as connecting and is interested in drawing while walking in the field, making marks whilst moving, using a variety of mediums to record, physically and literally, the body's movement through space. The artists' book looks at the relationship between this physical mark-making and language in the conventional sense of the word. This essay is a discussion and reflection of our processes, with a focus on conversation as collaboration and perceptions of ecosystems in this environment.
Abstract Background Chronic alcohol consumption reduces brain serotonin and alters the synaptic mechanisms involved in memory formation. Hippocampal 5-HT1A receptors modulate these mechanisms, but ...the neuroadaptive response of 5HT1A receptors to chronic alcohol self-administration is not well understood. Methods Hippocampal tissue from monkeys that voluntarily self-administered ethanol for 12 months ( n = 9) and accompanying controls ( n = 8) were prepared for in vitro receptor autoradiography and laser capture microdissection. The 5-HT1A receptor antagonist, 3 HMPPF, and the agonist, 3 H8-OH-DPAT, were used to measure total and G-protein coupled 5-HT1A receptors respectively. The expression of the genes encoding the 5-HT1A receptor and its trafficking protein Yif1B was measured in microdissected dentate gyrus (DG) granule cells and CA1 pyramidal neurons. Results An increase in G-protein coupled, but not total, receptors was observed in the posterior pyramidal cell layer of CA1 in ethanol drinkers compared to controls. Chronic ethanol self-administration was also associated with an up-regulation of total and G-protein coupled 5-HT1A receptors in the posterior DG polymorphic layer. Changes in receptor binding were not associated with concomitant changes in 5-HT1A receptor mRNA expression. Chronic ethanol self-administration was associated with a significant increase in Yif1B gene expression in posterior CA1 pyramidal neurons. Conclusions Chronic, ethanol self-administration up-regulates hippocampal 5-HT1A receptor density in a region-specific manner that does not appear to be due to alterations at the level of transcription but instead may be due to increased receptor trafficking. Further exploration of the mechanisms mediating chronic ethanol-induced 5-HT1A receptor up-regulation and how hippocampal neurotransmission is altered is warranted.
This paper looks at the writing retreat as a model for Creative Writing H.E. teaching. Initially, the retreat seems to offer a way of encouraging the deep-level learning helpful to students in the ...development of a writing life. If Creative Writing students benefit from the kind of heutagogical capability development associated with constructivist teaching, then the writing retreat, with its opportunities for independent work and thinking and for quiet time away from the constraints of the usual timetable and the pressures of everyday life, seems to have much to offer. However, considerations of assessment soon call the model to account. How should the writing produced on retreats be assessed? Can assessment requirements ever be managed in a way that doesn't counteract the freedom of the retreat? This paper draws on staff and student research gained from a Student Academic Partnership project and a level 5 Creative Writing retreat module in an attempt to answer these questions.
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