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Environmental Enrichment during Abstinence Reduces Oxycodone Seeking and c-Fos Expression in a Subpopulation of Medial Prefrontal Cortex Neurons. Drug Alcohol Depend 2024 Feb 01;255:111077

Date

01/16/2024

Pubmed ID

38228055

Pubmed Central ID

PMC10869844

DOI

10.1016/j.drugalcdep.2023.111077

Scopus ID

2-s2.0-85182578672 (requires institutional sign-in at Scopus site)

Abstract

BACKGROUND: Several preclinical studies have demonstrated that environmental enrichment (EE) during abstinence reduces drug seeking for psychostimulant and opioid drugs. Drug seeking is dependent on activity within the dorsomedial prefrontal cortex, and enrichment has been able to reduce drug seeking-associated increases in c-Fos in this region. In this study, we tested the hypothesis that EE during abstinence from oxycodone self-administration would reduce drug seeking and c-Fos immunoreactivity within the prefrontal cortex in a cell-type specific manner.

METHODS: Male rats self-administered oxycodone in two-hours sessions for three weeks, then underwent an initial drug seeking test under extinction conditions after one week of forced abstinence. Following this test, rats received either EE or remained individually housed in their home cage, then a second drug seeking test, with tissue collection immediately afterward.

RESULTS: Compared to rats in standard housing, environmentally enriched rats had lower oxycodone seeking. In the prelimbic and infralimbic prefrontal cortices, the number of c-Fos+ cells was reduced, and this reduction was predominantly in inhibitory cells neurons, as evidenced by a reduction in the proportion of c-Fos+ cells in GAD+, but not CamKII+ cells. There was also a robust positive relationship between the number of c-Fos+ cells and persistence of oxycodone seeking in both the PrL and IL.

CONCLUSIONS: These findings further support the effectiveness of enriched environments to reduce reactivity to drug-associated stimuli and contexts and provide a potential mechanism by which this occurs.

Author List

Glaeser B, Panariello V, Banerjee A, Olsen CM

Authors

Anjishnu Banerjee PhD Associate Professor in the Data Science Institute department at Medical College of Wisconsin
Christopher M. Olsen PhD Associate Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Animals
Drug-Seeking Behavior
Male
Neurons
Oxycodone
Prefrontal Cortex
Proto-Oncogene Proteins c-fos
Rats
Self Administration