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

Rajtarun Madangopal, Ph.D.

Hot Off the Press – July 7, 2021

Published in Neuropsychopharmacology by Rajtarun Madangopal and Bruce Hope, et al. in the NIDA IRP Neuronal Ensembles in Drug Addiction Section.

Discriminative stimuli (DSs) play an important and understudied role in the persistent susceptibility to drug relapse. They signal drug availability (DS+) or unavailability (DS-) and control drug seeking prior to relapse. We previously demonstrated persistent DS-controlled cocaine seeking for up to 300 abstinence days in rats. In the current study, we examined the behavioral mechanisms and neurobiological substrates within prelimbic and infralimbic subregions of the medial prefrontal cortex (mPFC) that underly this persistent drug-seeking behavior. Our data indicates that during abstinence, DS+ and DS- independently control the expression and suppression of DS-controlled drug seeking, and that DS-controlled cocaine seeking (but not DS-guided discriminated cocaine seeking or DS-controlled cocaine self-administration) is mediated by infralimbic (but not prelimbic) cortex activity, likely via a presynaptic mechanism.

Publication Information

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

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

In: Neuropsychopharmacology, 2021, ISBN: 1740-634X.

Abstract | Links

@article{cite-keyb,

title = {Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats},

author = {Rajtarun Madangopal and Leslie A Ramsey and Sophia J Weber and Megan B Brenner and Veronica A Lennon and Olivia R Drake and Lauren E Komer and Brendan J Tunstall and Jennifer M Bossert and Yavin Shaham and Bruce T Hope},

url = {https://pubmed.ncbi.nlm.nih.gov/34162997/},

doi = {10.1038/s41386-021-01067-6},

isbn = {1740-634X},

year  = {2021},

date = {2021-01-01},

journal = {Neuropsychopharmacology},

abstract = {Persistent susceptibility to cue-induced relapse is a cardinal feature of addiction. Discriminative stimuli (DSs) are one type of drug-associated cue that signal drug availability (DS+) or unavailability (DS−) and control drug seeking prior to relapse. We previously established a trial-based procedure in rats to isolate DSs from context, conditioned stimuli, and other drug-associated cues during cocaine self-administration and demonstrated DS-controlled cocaine seeking up to 300 abstinence days. The behavioral and neural mechanisms underlying trial-based DS-control of drug seeking have rarely been investigated. Here we show that following discrimination training in our trial-based procedure, the DS+ and DS−independently control the expression and suppression of cocaine seeking during abstinence. Using microinjections of GABAA + GABAB receptor agonists (muscimol + baclofen) in medial prefrontal cortex, we report that infralimbic, but not prelimbic, subregion of medial prefrontal cortex is critical to persistent DS-controlled relapse to cocaine seeking after prolonged abstinence, but not DS-guided discriminated cocaine seeking or DS-controlled cocaine self-admininstration. Finally, using ex vivo whole-cell recordings from pyramidal neurons in the medial prefrontal cortex, we demonstrate that the disruption of DS-controlled cocaine seeking following infralimbic cortex microinjections of muscimol+baclofen is likely a result of suppression of synaptic transmission in the region via a presynaptic mechanism of action.},

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pubstate = {published},

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}