Prior chronic alcohol exposure enhances Pavlovian-to-instrumental transfer

Shields, Chloe N.; Gremel, Christina M.

doi:10.1016/j.alcohol.2021.07.004

Cited by 11 publications

(24 citation statements)

References 59 publications

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“…main effect Fs <0.02, ps >0.05). Visual inspection of the data suggested that in non-DREADD control animals, difference scores were higher in CIE compared to Air mice, similar to our prior observations (Shields & Gremel, 2021). H3 activation appeared to increase PIT in Air mice, whereas H3 activation in CIE mice appeared to reduce the strength of PIT (Figure 4B).…”

Section: Experiments 1: Chemogenetic Inhibition Of Cea In Pitsupporting

confidence: 86%

“…In Experiment 2, four cohorts of mice were exposed to four rounds of EtOH vapor or air control with repeated withdrawal (Becker, 1994;Becker & Lopez, 2004;Griffin et al, 2009;Lopez & Becker, 2005;Lopez et al, 2014;Renteria et al, 2018Renteria et al, , 2020Shields & Gremel, 2021). Each round consisted of four consecutive days of 16 h of vapor exposure (EtOH or air) followed by an 8 h withdrawal period.…”

Section: Chronic Intermittent Etoh Exposurementioning

confidence: 99%

“…Tones were presented in alternating order, beginning with the CS+ tone, and lever presses and food port entries were recorded. Notably, this procedure results in relatively weak PIT in control mice (Shields & Gremel, 2021), allowing observation of PIT enhancement and reducing concern for ceiling effects.…”

Section: Pavlovian-to-instrumental Testingmentioning

confidence: 99%

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Effects of central amygdala chemogenetic manipulation and prior chronic alcohol exposure on Pavlovian‐to‐instrumental transfer

Shields

Gremel

2022

Alcoholism Clin & Exp Res

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Background Recent work suggests that a history of chronic alcohol exposure can enhance the influence of nondrug reward cues on ongoing actions. This is often modeled in Pavlovian‐to‐instrumental transfer (PIT) tasks that examine the interaction between Pavlovian and instrumental learning processes, usually reflected as an increase in action vigor during the presentation of a reward‐associated cue. Though prior chronic alcohol exposure strengthens this type of cue‐guided behavior, the neural mechanisms underlying such enhancements are not known. Methods In the present work, we examined the contribution of the central amygdala (CeA), a region strongly implicated in PIT behaviors and functionally altered by chronic alcohol exposure. We utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to examine the impact of inhibitory and excitatory CeA manipulation on PIT behaviors in alcohol‐naïve mice and mice with a history of chronic intermittent ethano vapor exposure and withdrawal (CIE). Results Replicating previous work, we found that a history of CIE strengthened baseline PIT, in the absence of any CeA manipulation. We also found that activation of both inhibitory and excitatory DREADDs expressed in CeA enhanced PIT in alcohol‐naïve mice, though the latter markedly reduced response rates. However, in mice exposed to CIE, activation of excitatory DREADD receptors expressed in CeA appeared to weaken PIT. Conclusions These results suggest that alcohol‐induced disruptions in amygdala function may contribute to changes in appetitive behaviors, such as cue‐guided responding, following chronic exposure to alcohol. Better elucidating the neural mechanisms that underlie disrupted cue‐guided behavior following chronic alcohol exposure may help to understand and treat deficits in adaptive behavior associated with chronic alcohol use in humans.

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Section: Experiments 1: Chemogenetic Inhibition Of Cea In Pitsupporting

confidence: 86%

Section: Chronic Intermittent Etoh Exposurementioning

confidence: 99%

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Effects of central amygdala chemogenetic manipulation and prior chronic alcohol exposure on Pavlovian‐to‐instrumental transfer

Shields

Gremel

2022

Alcoholism Clin & Exp Res

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“…Male Long-Evans rats ( N = 26) were obtained from Charles River and weighed > 290 g at the start of the study. Female rats were not used here to minimize variability, as previous studies have observed significant sex differences in reward consumption ( Marshall et al, 2017 ; Westbrook et al, 2018 ) and assays of incentive motivation ( Pitchers et al, 2015 ; Reichelt et al, 2016 ; Madayag et al, 2017 ; Tapia et al, 2019 ) including PIT ( Shields and Gremel, 2021 ; Derman and Lattal, 2022 ). Rats were paired-housed in transparent plastic cages in a temperature- and humidity-controlled vivarium.…”

Section: Methodsmentioning

confidence: 99%

Dorsomedial prefrontal cortex activation disrupts Pavlovian incentive motivation

Halbout

Hutson

Wassum

et al. 2022

Front. Behav. Neurosci.

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The dorsomedial prefrontal cortex (dmPFC) is known to make important contributions to flexible, reward-motivated behavior. However, it remains unclear if the dmPFC is involved in regulating the expression of Pavlovian incentive motivation, the process through which reward-paired cues promote instrumental reward-seeking behavior, which is modeled in rats using the Pavlovian-instrumental transfer (PIT) task. The current study examined this question using a bidirectional chemogenetic strategy in which inhibitory (hM4Di) or excitatory (hM3Dq) designer G-protein coupled receptors were virally expressed in dmPFC neurons, allowing us to later stimulate or inhibit this region by administering CNO prior to PIT testing. We found that dmPFC inhibition did not alter the tendency for a reward-paired cue to instigate instrumental reward-seeking behavior, whereas dmPFC stimulation disrupted the expression of this motivational influence. Neither treatment altered cue-elicited anticipatory activity at the reward-delivery port, indicating that dmPFC stimulation did not lead to more widespread motor suppression. A reporter-only control experiment indicated that our CNO treatment did not have non-specific behavioral effects. Thus, the dmPFC does not mediate the expression of Pavlovian incentive motivation but instead has the capacity to exert pronounced inhibitory control over this process, suggesting that it is involved in adaptively regulating cue-motivated behavior.

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“…Deficits in learning, discrimination or reactivity to non-alcohol cues have been reported after CIE vapor inhalation (Barker et al, 2016), especially after more prolonged CIE procedures in both rats and mice (DePoy et al, 2015;Natividad et al, 2018). Yet, CIE vapor inhalation has also been reported to enhance subsequent responding to non-alcohol cues by mice, including in tests of Pavlovian-to-instrumental transfer (Shields and Gremel, 2021), as well as pairwise visual discrimination and reversal learning (DePoy et al, 2013). At this point it is difficult to reconcile these disparate findings, but it is likely that both the duration and time since CIE vapor inhalation impact the direction of the effects, with longer and/or more recent exposure being more likely to produce deficits in cue-guided behavior and memory.…”

Section: Learning and Responsivity To Non-alcohol Cues Is Impacted By...mentioning

confidence: 99%

Alcohol availability during withdrawal gates the impact of alcohol vapor exposure on responses to alcohol cues

et al. 2022

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Background: Chronic intermittent ethanol (CIE) vapor inhalation is a widely used model of alcohol dependence, but the impact of CIE on cue-elicited alcohol seeking is not well understood. Here, we assessed the effects of CIE on alcohol-seeking elicited by previously learned cues, and on acquisition of new cue-alcohol associations. Methods:In Experiment 1, male and female Long Evans rats were first trained in a discriminative stimulus (DS) task, in which one auditory cue (the DS) predicts the availability of 15% ethanol and a control cue (the NS) predicts nothing. Rats then underwent CIE or served as controls. Subsets of each group received access to oral ethanol twice a week during acute withdrawal. After CIE, rats were presented with the DS and NS cues under extinction and retraining conditions to determine whether they would alter their responses to these cues. In Experiment 2, rats underwent CIE prior to training in the DS task. We also assessed alcohol consumption, aversion-resistant drinking, somatic withdrawal symptoms, and behavior in an open field. Results:We found that CIE enhanced behavioral responses to previously learned alcohol cues, but only in rats that received access to alcohol during acute withdrawal. CIE disrupted cue responses in rats that did not. When CIE occurred before cue learning, male rats were slower to develop cue responses and less likely to enter the alcohol port, even though they had received alcohol during acute withdrawal. We also found that CIE increased alcohol consumption and aversion-resistant drinking in male but not female rats.Conclusions: These results suggest that CIE alone does not potentiate the motivational value of alcohol cues, but that an increase in cue responses requires the potentiation of the value of alcohol during acute withdrawal. Further, under some conditions CIE may disrupt responses to previously learned and subsequently acquired alcohol cues.

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Prior chronic alcohol exposure enhances Pavlovian-to-instrumental transfer

Cited by 11 publications

References 59 publications

Effects of central amygdala chemogenetic manipulation and prior chronic alcohol exposure on Pavlovian‐to‐instrumental transfer

Effects of central amygdala chemogenetic manipulation and prior chronic alcohol exposure on Pavlovian‐to‐instrumental transfer

Dorsomedial prefrontal cortex activation disrupts Pavlovian incentive motivation

Alcohol availability during withdrawal gates the impact of alcohol vapor exposure on responses to alcohol cues

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