The role of anterior insula–brainstem projections and alpha-1 noradrenergic receptors for compulsion-like and alcohol-only drinking

Sergio, Thatiane De Oliveira; Lei, Kelly; Kwok, Claudina; Ghotra, Shahbaj; Wegner, Scott A.; Walsh, Margaret M.; Waal, Jaclyn; Darevsky, David; Hopf, F. Woodward

doi:10.1038/s41386-021-01071-w

Cited by 32 publications

(82 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In interesting concurrence, compulsion-like responding for alcohol in human AUD involves activation of a similar aINS-striatal circuits [37,38], and risk- and aversion-related responding more generally relates to aINS activity (reviewed in [28]). However, global inhibition of aINS can strongly impact AOD as well as CLAD ([34,39], consistent with insula/salience network importance for motivated behavior more generally [28-30,32,40], and suggesting that there could be parallel aINS-related mechanisms that differentially regulate AOD and CLAD (discussed in [34]). However, one major obstacle to understanding aINS importance for promoting alcohol consumption is the lack of information on in vivo aINS firing patterns, which could reveal critical and foundational insights into the nature of aINS activity that drives different aspects alcohol intake.…”

Section: Introductionmentioning

confidence: 79%

“…After 3-4 weeks LDA, rats had 2-3 days/wk of drinking alcohol with quinine, usually 2 sessions each of AQ10 and AQ60, in part to habituate to quinine assure that alcohol-quinine is not novel during experimental sessions. We widely use these methods [27,33,34,41,55,56]. We note that IA2BC rats can drink ~0.8 g/kg in a 20-min session, with BECs of ~40-50 mg/dL [33,57]; we consider CLAD less about intake levels per se, and more defined by the motivational processes (i.e., the decision to drink alcohol despite aversive consequences).…”

Section: Methodsmentioning

confidence: 99%

“…The aINS, a key regulator of the Salience Network, mediates rapid identification and responding to important situations [28–32], and human aINS is linked to many aspects of alcohol drinking [28] (see Discussion). Importantly, we have previously shown that specific aINS projections, aINS-Nucleus Accumbens Core (NAcb) [33] and aINS-Locus Coeruleus area [34], are essential for promoting CLAD in male rodents, with little impact on alcohol-only drinking (AOD), suggesting particular aINS importance for CLAD (see also [35,36]). In interesting concurrence, compulsion-like responding for alcohol in human AUD involves activation of a similar aINS-striatal circuits [37,38], and risk- and aversion-related responding more generally relates to aINS activity (reviewed in [28]).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, here we used 32-electrode multi-wire electrophysiology to record single-unit activity in right aINS from 15 rats during different alcohol drinking sessions, including AOnly, what we have termed moderate-challenge CLAD (AQ10, alcohol with 10 mg/L quinine), and higher-challenge CLAD (AQ60, alcohol with 60 mg/L quinine) [27,33,34,41]. We used quinine-resistant drinking, rather than footshock, since similar cortical-NAcb projections underlie both quinine- and footshock-resistant alcohol consumption [33], and higher shock-resistance correlates with higher quinine-resistance for alcohol [42,43].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Anterior insular cortex firing links initial and sustained encoding during aversion-resistant alcohol consumption

Starski

Morningstar

Katner

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Compulsive-like alcohol drinking (CLAD), where intake persists despite adverse consequences, is often a core facet of alcohol use disorder. Recent work sheds light on underlying mechanisms, but much remains unknown about CLAD etiology. Previously, we showed that projections from anterior insula (aINS), a central mediator of emotion, motivation, and interoception, promote CLAD in rodents, and heavy human drinkers exhibit similar insula-circuit recruitment under compulsion-like conditions. However, global aINS inhibition also reduces alcohol-only drinking (AOD), and one major obstacle is the lack of information on aINS firing patterns that could promote different aspects of intake. Here, we recorded single-unit activity in right aINS from 15 rats during AOD or CLAD (10mg/L or 60mg/L quinine in alcohol). Neurons with a sustained-increase or sustained-decrease phenotype (SIP, SDP) showed no firing differences across drinking conditions. In contrast, aINS neurons with a phenotype of strong firing increase at initiation of responding (IRP) showed significantly greater activity across the rest of licking during CLAD versus AOD, concurring with our previous behavioral findings suggesting quick evaluation and response strategy adjustment under CLAD. There were also no condition-related differences in firing-phenotype abundance. Further, total responding only correlated with abundance of SDP cells, but SDP firing returned to baseline during pauses in licking, while IRP and SIP sustained responding through pauses in licking. Thus, only aINS cells with a particular strong firing at licking onset showd greater sustained responding under compulsion-like conditions, while other cells likely promoted drinking more generally, providing critical new information about how aINS activity could promote alcohol consumption under different drinking conditions.

show abstract

Section: Introductionmentioning

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Anterior insular cortex firing links initial and sustained encoding during aversion-resistant alcohol consumption

Starski

Morningstar

Katner

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…2 In a recent literature review, Martella et al (2020) conclude that the symptoms of ADHD are largely due to a dysfunction of the LC-NE system (Bertollo and Berchicci, 2014). The anterior insula plays an important role in the locus coeruleusnorepinephrine (LC-NE) system (Aston-Jones and Cohen, 2005;Clewett et al, 2014;Harsay et al, 2018;De Oliveira Sergio et al, 2021). According to van der Linden et al (2021) the LC-NE system is a main factor in regulating activities characterized by intrinsic motivation.…”

Section: Attention and Motivationmentioning

confidence: 99%

Fluid Attention in Education: Conceptual and Neurobiological Framework

Bruya

Tang

2021

Front. Psychol.

View full text Add to dashboard Cite

Attention is indispensable to our learning, performance, relationships, health, and daily life, and yet laboratory studies of attention have only scratched the surface of these lived varieties of attention. In this article, we begin with William James' theory of derived involuntary attention, which has largely been ignored in laboratory research. We then show that there is a gap in our attention vocabulary and the theory that underpins it, which depend on an incomplete voluntary/involuntary dichotomy. The negative effects of this dichotomy stretch beyond laboratory research to clinical diagnosis, influencing how we understand so-called attention deficits. To fill the gap between voluntary and involuntary, we introduce a third kind of attention—fluid attention (also called postvoluntary attention), which is goal-directed and selective, like voluntary attention, but also effortless and drawn to its source, like involuntary attention. Fluid attention is a rediscovery of James' derived involuntary attention. A distinguishing feature of fluid attention is its motivational component, which, we show, neurophysiologically also reveals a gap in the neurocognitive literature on attention. Recognizing fluid attention as fundamentally motivational allows ADHD to be redefined as a motivational rather than an attentional deficit, which we go on to show has significant implications for both special and regular education.

show abstract

The maladaptive alcohol self‐administration task: An adapted novel model of alcohol seeking with negative consequences

Carlson

Weiner

2023

J Exper Analysis Behavior

View full text Add to dashboard Cite

The progression of recreational drinking to alcohol use disorder is characterized by loss of control over seeking, which involves continued use of alcohol despite negative consequences. The present study proposes a novel maladaptive alcohol self-administration task in which animals are trained to withhold alcohol drinking in the presence of an auditory cue signaling consequence (conflict phase) but to drink freely when there is no consequence (neutral phase). These phases are performed within trial; successful performance involves waiting for the conflict phase to end and drinking during the neutral phase. We discuss the background and implementation of the task, its relation to existing models, and its relevance to the field of translational alcohol research. Importantly, we also present evidence of its efficacy. Both male and female Long-Evans rats are capable of performing the maladaptive alcohol self-administration task for both sweetened and unsweetened alcohol solutions. Finally, we show that acute injection of a pharmacological stressor (yohimbine) significantly disrupted performance of the task in both sexes and reinforcers. We suggest the maladaptive alcohol self-administration task may prove particularly useful in models of alcohol use disorder or vulnerability to this disorder where its application may reveal maladaptive neural circuit adaptations responsible for motivational perturbations associated with loss of control over alcohol seeking.

show abstract

The role of anterior insula–brainstem projections and alpha-1 noradrenergic receptors for compulsion-like and alcohol-only drinking

Cited by 32 publications

References 82 publications

Anterior insular cortex firing links initial and sustained encoding during aversion-resistant alcohol consumption

Anterior insular cortex firing links initial and sustained encoding during aversion-resistant alcohol consumption

Fluid Attention in Education: Conceptual and Neurobiological Framework

The maladaptive alcohol self‐administration task: An adapted novel model of alcohol seeking with negative consequences

Contact Info

Product

Resources

About