Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats

Madangopal, Rajtarun; Ramsey, Leslie A.; Weber, Sophia J; Brenner, Megan B; Lennon, Veronica A; Drake, Olivia R; Komer, Lauren; Tunstall, Brendan J.; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.

doi:10.1038/s41386-021-01067-6

Cited by 19 publications

(9 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To our knowledge this is the first time that DSinduced reinstatement of alcohol seeking has been observed after punishment-imposed abstinence. While this study shows that a DS can act in a manner comparable to a context, another study recently found that a DS can induce relapse to cocaine seeking after abstinence (Madangopal et al, 2019(Madangopal et al, , 2021. Critically, Madangopal et al show that this relapse is potentiated in a manner comparable to incubation of drug seeking (Grimm et al, 2001), demonstrating an important difference between contextual and discriminative Cues.…”

Section: Role Of Discriminative Stimuli In Relapse To Alcohol Seeking After Punishmentmentioning

confidence: 51%

Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions

McDonald

Alonso-Lozares

Rauh

et al. 2021

Front. Behav. Neurosci.

View full text Add to dashboard Cite

In humans, stimuli associated with alcohol availability can provoke relapse during abstinence. In this study, we investigated the role of discriminative stimuli (DS) in the control of alcohol seeking in two types of behavioral tests. The first test examined the ability of an alcohol-associated DS to promote alcohol seeking (relapse) after punishment-imposed abstinence in the presence of a different DS. Following this, we tested whether the differentially associated DS can promote and suppress alcohol self-administration in a within-session discrimination task. During the within-session discrimination task, we also tested the rate of alcohol self-administration when two DS are presented in a compound. We first trained Long-Evans male rats (n = 24) to self-administer alcohol in the presence of one DS (reward-associated discriminative stimulus, rewDS) and then punished that behavior in the presence of a different DS (punishment-associated discriminative stimulus, punDS). On the test, we found that rats tested with the rewDS showed higher alcohol seeking than rats tested with the punDS. This result shows that a single Cue DS can promote alcohol seeking in a manner comparable to contexts. Subsequently, we trained 16 of these rats in a within-session trial-based discrimination task, comprised of intervening 2-min trials of rewDS, punDS, or conflict with rewDS and punDS in compound and a reduced probability of punishment. We found that alcohol self-administration is bi-directionally regulated by the rewDS and punDS. In conflict trials, alcohol self-administration was at a rate that was intermediate between the rewDS and punDS trials. In a final test, rats were presented with one of the three trial conditions and perfused for Fos immunohistochemistry. We found Fos expression was higher in the rats tested in the conflict condition in three interconnected sub-cortical brain regions. This study demonstrated the important role that alcohol-associated DS plays an important role in promoting relapse to alcohol seeking after punishment-imposed abstinence. We also implemented a within-session discrimination task that allows for the study of alcohol seeking under motivational conflict, which may be relevant for alcohol use despite negative consequences. The results from the Fos data suggest that higher alcohol seeking in approach-avoidance motivational conflict is associated with activation of sub-cortical regions but not cortical regions.

show abstract

Section: Role Of Discriminative Stimuli In Relapse To Alcohol Seeking After Punishmentmentioning

confidence: 51%

Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions

McDonald

Alonso-Lozares

Rauh

et al. 2021

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Baclofen and muscimol (B+M) are GABA A and GABA B agonists, respectively, often used together to inhibit neuronal activity via presynaptic or postsynaptic hyperpolarization. For example, in the PFC, B+M locally reduces neural activity by inhibiting the presynaptic input onto pyramidal cells, most likely, via activation of presynaptic GABA B receptors [ 60 ]. While powerful, there are several inherent disadvantages of pharmacological inactivation studies.…”

Section: Methods For Inhibiting Brain Regions and Circuitsmentioning

confidence: 99%

“…Activation of the IL with bicuculline and baclofen (GABA A and GABA B antagonists) increased cocaine seeking after 1 day of abstinence, while, after 30 days of abstinence, inactivation of IL with B+M attenuated the incubation of cocaine seeking [ 93 ]. Similarly, following 21 days of abstinence, intra-IL B+M inhibited cocaine-seeking when the stimulus light over the active (cocaine) lever was used as a discriminative stimulus instead of a response-contingent drug-paired cue [ 60 ]. Together, these studies suggest that IL is recruited by extinction training to inhibit cocaine seeking, and in the absence of such instrumental extinction, the IL drives cocaine-seeking.…”

Section: The Role Of the Pl Il And Ofc In Mediating Cocaine Reinstate...mentioning

confidence: 99%

The roles of rat medial prefrontal and orbitofrontal cortices in relapse to cocaine-seeking: A comparison across methods for identifying neurocircuits

Mesa

Wesson

Schwendt

et al. 2022

Addiction Neuroscience

View full text Add to dashboard Cite

“…By activating several of these pathways, we identified a particularly important role for ORB inputs to NAc in coordinating consumption of natural rewards. Although we focus on ORB, it is likely that other NAc inputs have important roles in other behavioral domains (57)(58)(59)(60). ORB is crucial for decision making and updating reward value based on internal states (61,62).…”

Section: Drugs and Natural Rewards Engage Similar Nac Inputsmentioning

confidence: 99%

Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need

Tan,

Browne,

Nöbauer

et al. 2024

Science

View full text Add to dashboard Cite

Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified Rheb as a molecular substrate that regulates cell type–specific signal transduction in NAc while enabling drugs to suppress natural reward consumption. Mapping NAc-projecting regions activated by drugs of abuse revealed input-specific effects on natural reward consumption. These findings characterize the dynamic, molecular and circuit basis of a common reward pathway, wherein drugs of abuse interfere with the fulfillment of innate needs.

show abstract

Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats

Cited by 19 publications

References 99 publications

Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions

Alcohol Seeking Under Risk of Punishment Is Associated With Activation of Cortical and Subcortical Brain Regions

The roles of rat medial prefrontal and orbitofrontal cortices in relapse to cocaine-seeking: A comparison across methods for identifying neurocircuits

Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need

Contact Info

Product

Resources

About