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      Regional Differences in Striatal Neuronal Ensemble Excitability Following Cocaine and Extinction Memory Retrieval in Fos-GFP Mice

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          Abstract

          Learned associations between drugs of abuse and the drug administration environment have an important role in addiction. In rodents, exposure to a drug-associated environment elicits conditioned psychomotor activation, which may be weakened following extinction (EXT) learning. Although widespread drug-induced changes in neuronal excitability have been observed, little is known about specific changes within neuronal ensembles activated during the recall of drug–environment associations. Using a cocaine-conditioned locomotion (CL) procedure, the present study assessed the excitability of neuronal ensembles in the nucleus accumbens core and shell (NAc core and NAc shell), and dorsal striatum (DS) following cocaine conditioning and EXT in Fos-GFP mice that express green fluorescent protein (GFP) in activated neurons (GFP+). During conditioning, mice received repeated cocaine injections (20 mg/kg) paired with a locomotor activity chamber (Paired) or home cage (Unpaired). Seven to 13 days later, both groups were re-exposed to the activity chamber under drug-free conditions and Paired, but not Unpaired, mice exhibited CL. In a separate group of mice, CL was extinguished by repeatedly exposing mice to the activity chamber under drug-free conditions. Following the expression and EXT of CL, GFP+ neurons in the NAc core (but not NAc shell and DS) displayed greater firing capacity compared to surrounding GFP− neurons. This difference in excitability was due to a generalized decrease in GFP− excitability following CL and a selective increase in GFP+ excitability following its EXT. These results suggest a role for both widespread and ensemble-specific changes in neuronal excitability following recall of drug–environment associations.

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          Author and article information

          Journal
          Neuropsychopharmacology
          Neuropsychopharmacology
          Neuropsychopharmacology
          Nature Publishing Group
          0893-133X
          1740-634X
          March 2018
          25 May 2017
          12 July 2017
          : 43
          : 4
          : 718-727
          Affiliations
          [1 ] Sussex Neuroscience, Sussex Addiction Research and Intervention Centre (SARIC), School of Psychology, University of Sussex , Falmer, UK
          Author notes
          [* ] CRPC 5.14, Sussex Neuroscience, Sussex Addiction Research and Intervention Centre (SARIC), School of Psychology, University of Sussex , Falmer, BN1 9QG, UK. Tel: +44 1276 877 776, E-mail: e.koya@ 123456sussex.ac.uk
          Author information
          http://orcid.org/0000-0002-7095-3371
          http://orcid.org/0000-0002-1885-2661
          http://orcid.org/0000-0002-5039-4875
          Article
          PMC5809776 PMC5809776 5809776 npp2017101
          10.1038/npp.2017.101
          5809776
          28540927
          373441de-596a-495d-ae47-6a0d6c4405e9
          Copyright © 2018 American College of Neuropsychopharmacology
          History
          : 17 March 2017
          : 03 May 2017
          : 18 May 2017
          Categories
          Original Article

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