Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats
| Autor: | Olivia R Drake, Bruce T. Hope, Jennifer M. Bossert, Leslie A. Ramsey, Veronica A Lennon, Brendan J. Tunstall, Rajtarun Madangopal, Megan B Brenner, Lauren E Komer, Sophia J Weber, Yavin Shaham |
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| Rok vydání: | 2021 |
| Předmět: |
media_common.quotation_subject
Drug-Seeking Behavior Infralimbic cortex Prefrontal Cortex Self Administration Context (language use) GABAB receptor Article Extinction Psychological Cocaine-Related Disorders 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cocaine Recurrence Animals Medicine Prefrontal cortex media_common Pharmacology business.industry GABAA receptor Abstinence Rats 030227 psychiatry Psychiatry and Mental health Baclofen medicine.anatomical_structure chemistry Muscimol Cues business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuropsychopharmacology |
| ISSN: | 1740-634X 0893-133X |
| Popis: | 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 GABA(A) + GABA(B) 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. |
| Databáze: | OpenAIRE |
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