Adolescent Alcohol Exposure Alters GABA A Receptor Subunit Expression in Adult Hippocampus

Fleming

Alcoholism Clin & Exp Res

et al. 2015

Self Cite

105

Background Human adolescence is a crucial stage of neurological development during which ethanol (EtOH) consumption is often at its highest. Alcohol abuse during adolescence may render individuals at heightened risk for subsequent alcohol abuse disorders, cognitive dysfunction, or other neurological impairments by irreversibly altering long-term brain function. To test this possibility, we modeled adolescent alcohol abuse (i.e., intermittent EtOH exposure during adolescence [AIE]) in rats to determine whether adolescent exposure to alcohol leads to long-term structural and functional changes that are manifested in adult neuronal circuitry. Methods We specifically focused on hippocampal area CA1, a brain region associated with learning and memory. Using electrophysiological, immunohistochemical, and neuroanatomical approaches, we measured post-AIE changes in synaptic plasticity, dendritic spine morphology, and synaptic structure in adulthood. Results We found that AIE-pretreated adult rats manifest robust long-term potentiation, induced at stimulus intensities lower than those required in controls, suggesting a state of enhanced synaptic plasticity. Moreover, AIE resulted in an increased number of dendritic spines with characteristics typical of immaturity. Immunohistochemistry-based analysis of synaptic structures indicated a significant decrease in the number of co-localized pre- and postsynaptic puncta. This decrease is driven by an overall decrease in 2 postsynaptic density proteins, PSD-95 and SAP102. Conclusions Taken together, these findings reveal that repeated alcohol exposure during adolescence results in enduring structural and functional abnormalities in the hippocampus. These synaptic changes in the hippocampal circuits may help to explain learning-related behavioral changes in adult animals preexposed to AIE.

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Adolescent Intermittent Alcohol Exposure: Persistence of Structural and Functional Hippocampal Abnormalities into Adulthood

Fleming

Alcoholism Clin & Exp Res

et al. 2015

Self Cite

105

“…Prior surface-expressed proteins used as controls (Na-K-ATPase) are well-known to be altered by ethanol exposure (Wang et al, 2009; Santos et al, 2017). Therefore, equal amounts of loaded protein samples were similarly quantified as elsewhere (Diaz et al, 2011; Centanni et al, 2014). Optical densities for cell surface receptors were normalized to matched water controls within the same blot.…”

Section: Methodsmentioning

confidence: 99%

Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure

et al. 2018

These findings demonstrate that AIE induces changes in OXT-R and AVP-R surface expression in the hypothalamus along with social anxiety-like alterations in male rats. These social anxiety-like alterations can be reversed either by activation of the OXT system or by suppression of the AVP system, data that support the hypothesis that social anxiety-like alterations induced by adolescent alcohol exposure in male rats are associated at least in part with an OXT/AVP imbalance.

Genes Brain and Behavior

“…In contrast, rats subjected to adolescent intermittent alcohol (AIE) exposure between PD 30 and PD46 showed a significant reduction in the δ subunit protein levels in the absence of any changes in mRNA, at both 48 h and 26 days after the last alcohol exposure (Centanni et al . ). The α4 subunit protein levels were significantly reduced, but mRNA levels were increased, 26 days (but not 48 h) after the last AIE exposure.…”

Section: Evidence For Gabaa Receptor Involvement In Addictionmentioning

confidence: 97%

GABA_A receptor subtype involvement in addictive behaviour

Stephens

King

Lambert

et al. 2016

GABA A receptors form the major class of inhibitory neurotransmitter receptors in the mammalian brain. This review sets out to summarize the evidence that variations in genes encoding GABA A receptor isoforms are associated with aspects of addictive behaviour in humans, while animal models of addictive behaviour also implicate certain subtypes of GABA A receptor. In addition to outlining the evidence for the involvement of specific subtypes in addiction, we summarize the particular contributions of these isoforms in control over the functioning of brain circuits, especially the mesolimbic system, and make a first attempt to bring together evidence from several fields to understanding potential involvement of GABA A receptor subtypes in addictive behaviour. While the weight of the published literature is on alcohol dependency, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour.Keywords: Alcohol, animal model, benzodiazepine, conduct disorder, electrophysiology, gene association, gene knockout, impulsivity, nucleus accumbens, psychostimulant, reward Received 31 May 2016, revised 19 July 2016, accepted for publication 15 August 2016Both human and animal studies have implicated GABA A receptors in addiction processes. This article sets out to review the evidence for GABA A receptor involvement in relation to alcoholism and addiction to other drugs of abuse. It will begin with a summary of the structure and function of GABA A receptors and their subtype diversity, before reviewing the human and animal literature providing genetic and behavioural evidence for the role of GABA A receptors in addictive behaviour. Finally, we will attempt to integrate these data into our understanding of addiction processes, and their underlying neurobiology. While the review concerns itself broadly with GABAergic systems and addictive behaviour, the weight of the published literature is on alcohol dependency. Nevertheless, the underlying principles outlined are relevant across a number of different aspects of addictive behaviour.