Age-related effects on the association between alcohol use, severity and resting-state fMRI:a rat study comparing adolescent-onset and adult-onset drinking

Adolescence is marked by neurodevelopmental changes that increase reward sensitivity, risk-taking, and behavioural control challenges, heightening the risk of alcohol use and dependence. Alcohol's impact on resting-state functional connectivity (RSFC) may explain this risk, though comparisons to adulthood remain limited. This study examined age-related differences in the association between RSFC and alcohol use severity in rats that initiated low or high voluntary alcohol consumption during adolescence or adulthood. Forty-two male rats were selected based on their alcohol consumption levels after two months of exposure: adolescent (PND42) onset low (N=12) and high drinking (N=7) rats, and adult (PND77) onset low (N=11) and high drinking (N=12) rats. RSFC was measured 4-10 days after exposure ceased, and group-ICA identified networks. Permutation tests assessed associations between onset age and use severity on RSFC. Low drinking was associated with increased RSFC within the salience network compared to high drinking. High adolescent onset alcohol consumption was associated with increased Default Mode Network (DMN) connectivity relative to low use. Connectivity in this area was generally stronger in adult compared to adolescent onset groups. An age group effect was observed, with overall higher DMN-thalamic connectivity in adult versus adolescent onset rats. In conclusion, high adolescent alcohol use was associated with increased DMN connectivity compared to low use, potentially reflecting altered self-referential processing or withdrawal susceptibility in adulthood. In adult-onset rats, the observed increases in DMN and DMN-thalamic connectivity may reflect developmental differences rather than alcohol exposure. These findings highlight the need for further research on DMN connectivity and its role in AUD risk and resilience, particularly regarding adolescent alcohol use, and the inclusion of a control group without alcohol access to better isolate the effects of alcohol consumption.</p

Amygdala 14-3-3ζ as a Novel Modulator of Escalating Alcohol Intake in Mice

Alcoholism is a devastating brain disorder that affects millions of people worldwide. The development of alcoholism is caused by alcohol-induced maladaptive changes in neural circuits involved in emotions, motivation, and decision-making. Because of its involvement in these processes, the amygdala is thought to be a key neural structure involved in alcohol addiction. However, the molecular mechanisms that govern the development of alcoholism are incompletely understood. We have previously shown that in a limited access choice paradigm, C57BL/6J mice progressively escalate their alcohol intake and display important behavioral characteristic of alcohol addiction, in that they become insensitive to quinine-induced adulteration of alcohol. This study used the limited access choice paradigm to study gene expression changes in the amygdala during the escalation to high alcohol consumption in C57BL/6J mice. Microarray analysis revealed that changes in gene expression occurred predominantly after one week, i.e. during the initial escalation of alcohol intake. One gene that stood out from our analysis was the adapter protein 14-3-3ζ, which was up-regulated during the transition from low to high alcohol intake. Independent qPCR analysis confirmed the up-regulation of amygdala 14-3-3ζ during the escalation of alcohol intake. Subsequently, we found that local knockdown of 14-3-3ζ in the amygdala, using RNA interference, dramatically augmented alcohol intake. In addition, knockdown of amygdala 14-3-3ζ promoted the development of inflexible alcohol drinking, as apparent from insensitivity to quinine adulteration of alcohol. This study identifies amygdala 14-3-3ζ as a novel key modulator that is engaged during escalation of alcohol use

Animal models of alcohol and drug dependence

Drug addiction has serious health and social consequences. In the last 50 years, a wide range of techniques have been developed to model specific aspects of drug-taking behaviors and have greatly contributed to the understanding of the neurobiological basis of drug abuse and addiction. In the last two decades, new models have been proposed in an attempt to capture the more genuine aspects of addiction-like behaviors in laboratory animals. The goal of the present review is to provide an overview of the preclinical procedures used to study drug abuse and dependence and describe recent progress that has been made in studying more specific aspects of addictive behavior in animals.Universidade Estadual Paulista School of Pharmaceutical SciencesUniversidade Estadual Paulista School of Pharmaceutical Science

Correction:How the COVID-19 pandemic highlights the necessity of animal research (vol 30, pg R1014, 2020)

(Current Biology 30, R1014–R1018; September 21, 2020) As a result of an author oversight in the originally published version of this article, a number of errors were introduced in the author list and affiliations. First, the middle initials were omitted from the names of several authors. Second, the surname of Dr. van Dam was mistakenly written as “Dam.” Third, the first name of author Bernhard Englitz was misspelled as “Bernard” and the surname of author B.J.A. Pollux was misspelled as “Pullox.” Finally, Dr. Keijer's first name was abbreviated rather than written in full. These errors, as well as various errors in the author affiliations, have now been corrected online

The continued need for animals to advance brain research

Policymakers aim to move toward animal-free alternatives for scientific research and have introduced very strict regulations for animal research. We argue that, for neuroscience research, until viable and translational alternatives become available and the value of these alternatives has been proven, the use of animals should not be compromised