D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner

Caitlin V Cosme; Andrea L Gutman; Wensday R Worth; Ryan T LaLumiere

doi:10.1111/adb.12442

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D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner

Journal article

Peer reviewed

D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner

Caitlin V Cosme, Andrea L Gutman, Wensday R Worth and Ryan T LaLumiere

Addiction biology, Vol.23(1), pp.16-27

01/2018

DOI: 10.1111/adb.12442

PMCID: PMC5332541

PMID: 27578356

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https://www.ncbi.nlm.nih.gov/pmc/articles/5332541View

Open Access

Abstract

Evidence suggests that the infralimbic cortex (IL), a subregion of the ventromedial prefrontal cortex (vmPFC), suppresses cocaine-seeking behavior in a self-administration paradigm, whereas the more anterior vmPFC subregion, the medial orbitofrontal cortex (mOFC), has received very little attention in this regard. Despite the established dopaminergic innervation of the vmPFC, whether dopamine receptor blockade in each subregion alters the reinstatement of cocaine seeking is unclear. To address this issue, male Sprague-Dawley rats underwent 2 weeks of cocaine self-administration, followed by extinction training and reinstatement testing. Immediately prior to each reinstatement test, rats received microinjections of the D1 receptor antagonist SCH 23390, the D2 receptor antagonist sulpiride or their respective vehicles. D1 receptor blockade in the IL reduced cued reinstatement but had no effect on cocaine prime and cue + cocaine-prime reinstatement, whereas D2 receptor blockade in the IL had no effect on reinstatement. For the mOFC, however, D1 receptor blockade reduced cocaine seeking in all reinstatement types, whereas blocking D2 receptors in the mOFC had no effect on any form of cocaine seeking. These findings suggest different roles for D1 receptors in the IL versus the mOFC in regulating cocaine-seeking behavior. Moreover, even as previous work indicates that IL inactivation does not affect reinstatement but, rather, induces cocaine seeking during extinction, the present findings suggest that dopamine receptor activation in the IL is necessary for cocaine seeking under some circumstances.

Cues

Receptors, Dopamine D1 - antagonists & inhibitors

Sulpiride - pharmacology

Rats

Male

Benzazepines - pharmacology

Rats, Sprague-Dawley

Drug-Seeking Behavior - drug effects

Dopamine Uptake Inhibitors - administration & dosage

Cocaine - administration & dosage

Self Administration

Animals

Prefrontal Cortex - drug effects

Dopamine Antagonists - pharmacology

Extinction, Psychological

Receptors, Dopamine D2

Dopamine D2 Receptor Antagonists - pharmacology

Behavior, Animal - drug effects

Conditioning, Operant

Details

Title: Subtitle: D1, but not D2, receptor blockade within the infralimbic and medial orbitofrontal cortex impairs cocaine seeking in a region-specific manner
Creators: Caitlin V Cosme - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA
Andrea L Gutman - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA
Wensday R Worth - Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA
Ryan T LaLumiere - Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Addiction biology, Vol.23(1), pp.16-27
DOI: 10.1111/adb.12442
PMID: 27578356
PMCID: PMC5332541
NLM abbreviation: Addict Biol
ISSN: 1355-6215
eISSN: 1369-1600
Publisher: United States
Grant note: R01 DA034684 / NIDA NIH HHS
Language: English
Date published: 01/2018
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute
Record Identifier: 9984070612302771

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11 Times Cited - Web of Science