Flood-conditioned place aversion as a novel non-pharmacological aversive learning procedure in mice

Goltseker, Koral; Barak, Segev

doi:10.1038/s41598-018-25568-5

Cited by 14 publications

(17 citation statements)

References 52 publications

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“…Recently, we developed a two‐phase procedure in which CPP was induced by cocaine and was then counteracted in a lithium chloride (LiCl) CPA procedure 16 . Here, we applied a nonpharmacological aversive stimulus (water flood 29 ) as an alternative to LiCl, implicated in memory processing 16,35 …”

Section: Resultsmentioning

confidence: 99%

“…Mice were then returned to their home cages and held in a service room adjoined to the experiment room. Counterconditioning sessions started 45 min later and lasted 15 min, with a water flood aversion, as we previously described 29 . Thus, mice were placed in the alcohol‐paired compartment, which was then flooded with water (18ºC) to approximately 2 cm of height.…”

Section: Methodsmentioning

confidence: 99%

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Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

2020

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Relapse to alcohol abuse is often caused by exposure to potent alcohol‐associated cues. Therefore, disruption of the cue‐alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval and then restabilize within 6 h during a “reconsolidation” process. We recently showed that relapse to cocaine seeking in a place‐conditioning paradigm could be prevented by counterconditioning the cocaine cues with aversive outcomes following cocaine‐memory retrieval. However, to better model addiction‐related behaviors, self‐administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcohol‐memory reconsolidation, in the place conditioning and operant self‐administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol‐conditioned place preference was abolished only when aversive counterconditioning with water flooding was given shortly after alcohol‐memory retrieval. Furthermore, rats trained to lever press for alcohol showed decreased context‐induced renewal of alcohol‐seeking responding when the lever pressing was punished with foot‐shocks, shortly, but not 6 h, after memory retrieval. These results suggest that aversive counterconditioning can prevent relapse to alcohol seeking only when performed during alcohol‐memory reconsolidation, presumably by updating, or replacing, the alcohol memory with aversive information. Finally, we found that aversive counterconditioning preceded by alcohol‐memory retrieval was characterized by the upregulation of brain‐derived neurotrophic factor (Bdnf) mRNA expression in the medial prefrontal cortex, suggesting that BDNF may play a role in the memory updating process.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

2020

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“…Here, we applied a non-pharmacological aversive stimulus (water flood (Goltseker and Barak, 2018)) as an alternative to LiCl, since the pharmacological effects of the latter have been implicated in synaptic plasticity (Basselin et al, 2006), memory formation (Dewachter et al, 2009), memory reconsolidation (Wu et al, 2011), and memory extinction (Goltseker et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

“…Mice were placed in the alcoholpaired compartment, and shortly after the session started, two liters of water (18-20°C) were poured into the opposite (unpaired) compartment. As a result, water flowed under the sliding door and gradually flooded the paired compartment (where the mouse was located) to ~2 cm height (for the detailed description of the procedure see Goltseker and Barak, 2018). Mice from the Retrieval group remained in the compartment for 12 min, whereas mice from the No Retrieval group -for…”

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confidence: 99%

Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

Goltseker

Handrus

Barak

2019

Preprint

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Relapse to alcohol abuse is often caused by exposure to potent alcohol-associated cues. Therefore, disruption of the cue-alcohol memory can prevent relapse. It is believed that memories destabilize and become prone for updating upon their reactivation through retrieval, and then re-stabilize within 6 h during a "reconsolidation" process. We recently showed that relapse to cocaine seeking could be prevented by counterconditioning the cocaine-cues with aversive outcomes following cocaine-memory retrieval, in a place conditioning paradigm. However, to better model addictionrelated behaviors, self-administration models are necessary. Here, we demonstrate that relapse to alcohol seeking can be prevented by aversive counterconditioning conducted during alcoholmemory reconsolidation, in conditioned place preference (CPP) and operant self-administration paradigms, in mice and rats, respectively. We found that the reinstatement of alcohol-CPP was abolished only when aversive counterconditioning with water-flooding was given shortly after alcohol-memory retrieval. Furthermore, rats trained to lever-press for alcohol showed decreased context-induced renewal of alcohol-seeking responding when the lever-pressing was counterconditioned with foot-shocks, shortly, but not 6 h, after memory retrieval. These results 0suggest that aversive counterconditioning can prevent relapse to alcohol seeking only when performed during alcohol-memory reconsolidation, presumably by updating, or replacing, the alcohol memory with aversive information. Also, we found that aversive counterconditioning preceded by alcohol-memory retrieval was characterized by upregulation of brain-derived neurotrophic factor (Bdnf) mRNA expression in the medial prefrontal cortex, suggesting that Bdnf plays a role in the memory updating process. Operant self-administration, Conditioned place preference, BDNFAlcohol place conditioning (days 2-9): Training started 24 h after the Baseline test with one session per day over 8 days, with the sliding door closed. On days 3, 5, 7, and 9, mice were administered with alcohol (1.8 g/kg; i.p.) and immediately confined to the paired compartment for 5 min. On the alternate days (days 2, 4, 6, and 8), mice were administered with saline and were confined to the unpaired compartment for the same duration as on the alcohol-conditioning day.Paired compartments were counterbalanced.Place preference test 1 (day 10): Place preference test was identical to the Baseline stage, and served to index alcohol-CPP (Cunningham et al., 2003). Preference was defined as an increase in the percent of time spent in the alcohol-paired compartment during the Place preference test 1 compared to the Baseline test. Mice that did not show CPP (minimum of 5% change) were excluded from the experiment (3 from Experiment 1; 4 from Experiment 2).Memory retrieval and aversive counterconditioning (days 11-14). Prior to this stage, mice were assigned to different experimental conditions, Retrieval and No Retrieval (matched for CPP scores and sex). Training began 2...

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“…Another possibility would be to “show” the mice that the feeding place is refilled. This would be inspired by conditioned place preference and the study of Goltseker and Barak (2018): Here, conditioned place aversion was only induced when mice where placed in an empty compartment first, and then experienced the onset of the aversive stimulus (in this case: cold water flooding). Conditioned place aversion was not induced when the mice were placed in an already flooded compartment (Goltseker and Barak 2018).…”

Section: Discussionmentioning

confidence: 99%

Alternate without alternative: Neither preference nor simple learning behaviour shown by C57BL/6J mice in the T-maze

Habedank

Kahnau

Lewejohann

2020

Preprint

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In rodents, the T-maze test is commonly used to investigate spontaneous alternating behaviour but it can also be used to investigate memory, stimuli discrimination or preference between goods. However, especially regarding T-maze preference tests there is no recommended protocol and researchers frequently report reproduction difficulties of this test using mice.Here, we aimed to develop an efficient protocol with female C57BL/6J mice, conducting two preference tests with different design: In a first test, on two consecutive days with five trials, thirteen mice had to choose between two fluids. In a second preference test, on five consecutive days with two (week 1) or three (week 2) trials, twelve mice had to choose between one arm containing bedding mixed with millet and one containing only bedding. This test design resembled a simple learning test (learn where to find the rewarded and the unrewarded arm on the basis of spatial, olfactory and visual cues).In both experiments, mice took only a few seconds per trial to run the maze and make their choice. However, in both experiments mice failed to show any preference for one of the arms. Instead, they alternated choices. We therefore believe the T-maze test to be rather unsuitable to test preference or learning behaviour with C57BL/6J mice.

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Flood-conditioned place aversion as a novel non-pharmacological aversive learning procedure in mice

Cited by 14 publications

References 52 publications

Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

Disruption of relapse to alcohol seeking by aversive counterconditioning following memory retrieval

Alternate without alternative: Neither preference nor simple learning behaviour shown by C57BL/6J mice in the T-maze

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