Journal article
Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala
The Journal of neuroscience, v 37(17), pp 4462-4471
26 Apr 2017
PMID: 28336571
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The ability to inhibit drinking is a significant challenge for recovering alcoholics, especially in the presence of alcohol-associated cues. Previous studies have demonstrated that the regulation of cue-guided alcohol seeking is mediated by the basolateral amygdala (BLA), nucleus accumbens (NAc), and medial prefrontal cortex (mPFC). However, given the high interconnectivity between these structures, it is unclear how mPFC projections to each subcortical structure, as well as projections between BLA and NAc, mediate alcohol-seeking behaviors. Here, we evaluate how cortico-striatal, cortico-amygdalar, and amygdalo-striatal projections control extinction and relapse in a rat model of alcohol seeking. Specifically, we used a combinatorial viral technique to express diphtheria toxin receptors in specific neuron populations based on their projection targets. We then used this strategy to create directionally selective ablations of three distinct pathways after acquisition of ethanol self-administration but before extinction and reinstatement. We demonstrate that ablation of mPFC neurons projecting to NAc, but not BLA, blocks cue-induced reinstatement of alcohol seeking and neither pathway is necessary for extinction of responding. Further, we show that ablating BLA neurons that project to NAc disrupts extinction of alcohol approach behaviors and attenuates reinstatement. Together, these data provide evidence that the mPFC→NAc pathway is necessary for cue-induced reinstatement of alcohol seeking, expand our understanding of how the BLA→NAc pathway regulates alcohol behavior, and introduce a new methodology for the manipulation of target-specific neural projections.
The vast majority of recovering alcoholics will relapse at least once and understanding how the brain regulates relapse will be key to developing more effective behavior and pharmacological therapies for alcoholism. Given the high interconnectivity of cortical, striatal, and limbic structures that regulate alcohol intake, it has been difficult to disentangle how separate projections between them may control different aspects of these complex behaviors. Here, we demonstrate a new approach for noninvasively ablating each of these pathways and testing their necessity for both extinction and relapse. We show that inputs to the nucleus accumbens from medial prefrontal cortex and amygdala regulate alcohol-seeking behaviors differentially, adding to our understanding of the neural control of alcoholism.
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Details
- Title
- Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala
- Creators
- Colby R Keistler - 1Department of Psychiatry, Division of Molecular Psychiatry,Emma Hammarlund - Department of Psychiatry, Division of Molecular Psychiatry.Jacqueline M Barker - Medical University of South CarolinaColin W Bond - 1Department of Psychiatry, Division of Molecular Psychiatry,Ralph J DiLeone - 1Department of Psychiatry, Division of Molecular Psychiatry,Christopher Pittenger - Yale UniversityJane R Taylor - Yale University
- Publication Details
- The Journal of neuroscience, v 37(17), pp 4462-4471
- Publisher
- Society for Neuroscience
- Grant note
- R01 MH091861 / NIMH NIH HHS R01 DK098994 / NIDDK NIH HHS UL1 TR001863 / NCATS NIH HHS F31 AA024673 / NIAAA NIH HHS P50 AA012870 / NIAAA NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:000401038400005
- Scopus ID
- 2-s2.0-85019114754
- Other Identifier
- 991020100188004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences