Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α4/δ GABAA Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice

Sanna, Enrico; Talani, Giuseppe; Obili, Nicola; Mascia, Maria Paola; Mostallino, Maria Cristina; Secci, Pietro Paolo; Pisu, Maria Giuseppina; Biggio, Francesca; Utzeri, C; Olla, Pierluigi; Biggio, Giovanni; Follesa, Paolo

doi:10.3389/fnins.2011.00015

Cited by 45 publications

(82 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In agreement with these findings, maternal separation in rodents is known to induce persistent increases in alcohol consumption in adulthood (Roman et al, 2005;Cruz et al, 2008;Nylander and Roman, 2013). Furthermore, postweaning isolation rearing in rodents has repeatedly been shown to result in augmented alcohol consumption and operant responding for alcohol in adulthood (Ellison, 1981;Schenk et al, 1990;Wolffgramm, 1990;Hall et al, 1998;Lodge and Lawrence, 2003;Advani et al, 2007;Deehan et al, 2007;McCool and Chappell, 2009;Sanna et al, 2011;Chappell et al, 2013;Butler et al, 2014).…”

Section: Introductionmentioning

confidence: 51%

“…Social isolation after weaning has been shown to enhance alcohol consumption in previous studies in rats and mice (Ellison, 1981;Schenk et al, 1990;Wolffgramm, 1990;Hall et al, 1998;Lodge and Lawrence, 2003;Advani et al, 2007;Deehan et al, 2007;McCool and Chappell, 2009;Sanna et al, 2011;Chappell et al, 2013;Butler et al, 2014). Importantly, however, in these studies, the animals were reared in isolation from weaning onwards.…”

Section: Discussionmentioning

confidence: 85%

“…Varlinskaya et al, 2001;Varlinskaya and Spear, 2002;Trezza et al, 2009) and the sensitivity to the facilitating effects of acute alcohol on social play behaviour seems to influence the amount of alcohol consumption during adolescence in a sex-dependent manner (Varlinskaya et al, 2015). Postweaning social isolation rearing has been shown to enhance alcohol consumption in rats and mice (Ellison, 1981;Schenk et al, 1990;Wolffgramm, 1990;Hall et al, 1998;Lodge and Lawrence, 2003;Advani et al, 2007;McCool and Chappell, 2009;Sanna et al, 2011;Chappell et al, 2013;Butler et al, 2014). However, these animals were reared in isolation from weaning onward, which leaves the question of whether deprivation of social play behaviour contributed towards the increase in alcohol consumption.…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Early social isolation augments alcohol consumption in rats

Lesscher

Spoelder

Rotte

et al. 2015

Behavioural Pharmacology

View full text Add to dashboard Cite

There is a considerable degree of individual vulnerability for alcohol use disorder (AUD) as only a subpopulation of individuals who regularly consume alcohol develop AUD. It is therefore very important to understand the factors and mechanisms that contribute towards the individual risk for AUD. In this respect, social influences, in particular during development, may be relevant for AUD as disruptions in early social experiences are associated with an increased risk for AUD. Social play, the most prominent form of social behaviour shown by young mammals, is rewarding and considered to be important for social, emotional and cognitive development. Recent studies suggest that early social isolation, effectively depriving animals from social play, increases the risk for addictive behaviour. The aim of this study was therefore to explore the long-term consequences of early social isolation on alcohol consumption and motivation for alcohol. To this end, rats were socially isolated from postnatal days 21-42, followed by 4 weeks of social housing, and voluntary alcohol consumption and operant responding for alcohol were determined in adulthood. We observed enhanced levels of alcohol consumption in adulthood in previously isolated rats, whereas operant responding for alcohol was not altered. The impact of early social isolation was independent of the individual variation in alcohol consumption. These data indicate that social isolation, during a developmental period when social play is highly abundant, enhances the propensity to consume alcohol in adulthood. This implies that early social experience may be a protective factor against excessive alcohol use.

show abstract

Section: Introductionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Early social isolation augments alcohol consumption in rats

Lesscher

Spoelder

Rotte

et al. 2015

Behavioural Pharmacology

View full text Add to dashboard Cite

show abstract

“…Coronal brain slices containing the NAcc shell region were prepared as previously described for hippocampus (67). For all recordings performed in MSNs of the Nacc shell, the temperature of the bath was maintained at 33°C.…”

Section: Methodsmentioning

confidence: 99%

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Spiga

Talani

Mulas

et al. 2014

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

Self Cite

View full text Add to dashboard Cite

Alcoholism involves long-term cognitive deficits, including memory impairment, resulting in substantial cost to society. Neuronal refinement and stabilization are hypothesized to confer resilience to poor decision making and addictive-like behaviors, such as excessive ethanol drinking and dependence. Accordingly, structural abnormalities are likely to contribute to synaptic dysfunctions that occur from suddenly ceasing the use of alcohol after chronic ingestion. Here we show that ethanol-dependent rats display a loss of dendritic spines in medium spiny neurons of the nucleus accumbens (Nacc) shell, accompanied by a reduction of tyrosine hydroxylase immunostaining and postsynaptic density 95-positive elements. Further analysis indicates that "long thin" but not "mushroom" spines are selectively affected. In addition, patch-clamp experiments from Nacc slices reveal that long-term depression (LTD) formation is hampered, with parallel changes in field potential recordings and reductions in NMDA-mediated synaptic currents. These changes are restricted to the withdrawal phase of ethanol dependence, suggesting their relevance in the genesis of signs and/or symptoms affecting ethanol withdrawal and thus the whole addictive cycle. Overall, these results highlight the key role of dynamic alterations in dendritic spines and their presynaptic afferents in the evolution of alcohol dependence. Furthermore, they suggest that the selective loss of long thin spines together with a reduced NMDA receptor function may affect learning. Disruption of this LTD could contribute to the rigid emotional and motivational state observed in alcohol dependence.A lcohol addiction is a major public health problem in the Western world. In the United States alone, about 15% of adults have an alcohol-related disorder at some point in their life, and alcohol abuse costs the economy over $220 billion per y in medical care and productivity loss (1). A general consensus has emerged on drug addiction as a substance-induced, aberrant form of neural plasticity (2, 3). The nucleus accumbens (Nacc) plays a central role in the neural circuits that are responsible for goal-directed behaviors (4, 5) and in addictive states. Its activity is heavily modulated by glutamate-(GLU) and dopamine-(DA) containing projections that originate in cortical and limbic regions and converge on a common postsynaptic target: the medium spiny neuron (MSN). Furthermore, DA modulates GLU inputs to Nacc neurons (6, 7), both by directly influencing synaptic transmission and by modulating voltage-dependent conductances (8). Accordingly, interactions between DA and GLU are involved in druginduced locomotor stimulation and addiction (9, 10) and may represent useful potential therapeutic targets (11,12). In the distal portion of the dendrites of MSNs a significant subpopulation of spines shows a particular synaptic architecture, called the "striatal microcircuit" or "synaptic triad" (13, 14), which is characterized by a double, discrete, and reciprocal interaction between DA and GLU aff...

show abstract

“…EtOH consumption (<10% EtOH) could induce an increase of GABA A R α4/δ subunits in the hippocampus in socially isolated C57BL/6J mice and rats [77,78] . These α4/δ-containing GABA A Rs have been shown to exist on extrasynaptic membrane sites, which are sensitive to as low as 3 mmol/L EtOH (approximately 0.3% EtOH) [79] .…”

Section: Effects Of Social Drinkingmentioning

confidence: 97%

Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors

2014

View full text Add to dashboard Cite

Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and crossaddiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABA A receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABA A receptors in the treatment of AUD and currently available and potentially novel pharmacological agents.

show abstract

Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α4/δ GABAA Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice

Cited by 45 publications

References 78 publications

Early social isolation augments alcohol consumption in rats

Early social isolation augments alcohol consumption in rats

Hampered long-term depression and thin spine loss in the nucleus accumbens of ethanol-dependent rats

Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors

Contact Info

Product

Resources

About