Environmental Enrichment During Abstinence Reduces Oxycodone Seeking and C-Fos Expression in a Subpopulation of Medial Prefrontal Cortex Neurons

Overview

Journal Drug Alcohol Depend

Publisher Elsevier

Specialty Psychiatry

Date 2024 Jan 16

PMID 38228055

Authors

Breanna Glaeser

Valeria Panariello

Anjishnu Banerjee

Christopher M Olsen

Affiliations

Soon will be listed here.

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.

References

Carroll M, Anker J, Perry J . Modeling risk factors for nicotine and other drug abuse in the preclinical laboratory. Drug Alcohol Depend. 2009; 104 Suppl 1:S70-8. DOI: 10.1016/j.drugalcdep.2008.11.011. View

Venniro M, Zhang M, Caprioli D, Hoots J, Golden S, Heins C . Volitional social interaction prevents drug addiction in rat models. Nat Neurosci. 2018; 21(11):1520-1529. PMC: 7386559. DOI: 10.1038/s41593-018-0246-6. View

Malone S, Shaykin J, Stairs D, Bardo M . Neurobehavioral effects of environmental enrichment and drug abuse vulnerability: An updated review. Pharmacol Biochem Behav. 2022; 221:173471. PMC: 10189610. DOI: 10.1016/j.pbb.2022.173471. View

Thiel K, Pentkowski N, Peartree N, Painter M, Neisewander J . Environmental living conditions introduced during forced abstinence alter cocaine-seeking behavior and Fos protein expression. Neuroscience. 2010; 171(4):1187-96. PMC: 3010380. DOI: 10.1016/j.neuroscience.2010.10.001. View

Melzer S, Monyer H . Diversity and function of corticopetal and corticofugal GABAergic projection neurons. Nat Rev Neurosci. 2020; 21(9):499-515. DOI: 10.1038/s41583-020-0344-9. View

Ranaldi R, Kest K, Zellner M, Hachimine-Semprebom P . Environmental enrichment, administered after establishment of cocaine self-administration, reduces lever pressing in extinction and during a cocaine context renewal test. Behav Pharmacol. 2011; 22(4):347-53. DOI: 10.1097/FBP.0b013e3283487365. View

McGlinchey E, James M, Mahler S, Pantazis C, Aston-Jones G . Prelimbic to Accumbens Core Pathway Is Recruited in a Dopamine-Dependent Manner to Drive Cued Reinstatement of Cocaine Seeking. J Neurosci. 2016; 36(33):8700-11. PMC: 4987439. DOI: 10.1523/JNEUROSCI.1291-15.2016. View

Willcocks A, McNally G . The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats. Eur J Neurosci. 2012; 37(2):259-68. DOI: 10.1111/ejn.12031. View

Muelbl M, Glaeser B, Shah A, Chiariello R, Nawarawong N, Stemper B . Repeated blast mild traumatic brain injury and oxycodone self-administration produce interactive effects on neuroimaging outcomes. Addict Biol. 2022; 27(2):e13134. PMC: 8896287. DOI: 10.1111/adb.13134. View

10.

Grimm J, Weber R, Barnes J, Koerber J, Dorsey K, Glueck E . Brief exposure to novel or enriched environments reduces sucrose cue-reactivity and consumption in rats after 1 or 30 days of forced abstinence from self-administration. PLoS One. 2013; 8(1):e54164. PMC: 3546924. DOI: 10.1371/journal.pone.0054164. View

11.

Pickens C, Airavaara M, Theberge F, Fanous S, Hope B, Shaham Y . Neurobiology of the incubation of drug craving. Trends Neurosci. 2011; 34(8):411-20. PMC: 3152666. DOI: 10.1016/j.tins.2011.06.001. View

12.

Caputi A, Melzer S, Michael M, Monyer H . The long and short of GABAergic neurons. Curr Opin Neurobiol. 2013; 23(2):179-86. DOI: 10.1016/j.conb.2013.01.021. View

13.

van den Oever M, Lubbers B, Goriounova N, Li K, van der Schors R, Loos M . Extracellular matrix plasticity and GABAergic inhibition of prefrontal cortex pyramidal cells facilitates relapse to heroin seeking. Neuropsychopharmacology. 2010; 35(10):2120-33. PMC: 3055295. DOI: 10.1038/npp.2010.90. View

14.

Solinas M, Chauvet C, Lafay-Chebassier C, Jaafari N, Thiriet N . Environmental enrichment-inspired pharmacological tools for the treatment of addiction. Curr Opin Pharmacol. 2020; 56:22-28. DOI: 10.1016/j.coph.2020.09.001. View

15.

Green T, Gehrke B, Bardo M . Environmental enrichment decreases intravenous amphetamine self-administration in rats: dose-response functions for fixed- and progressive-ratio schedules. Psychopharmacology (Berl). 2002; 162(4):373-8. DOI: 10.1007/s00213-002-1134-y. View

16.

Bozarth M, Murray A, Wise R . Influence of housing conditions on the acquisition of intravenous heroin and cocaine self-administration in rats. Pharmacol Biochem Behav. 1989; 33(4):903-7. DOI: 10.1016/0091-3057(89)90490-5. View

17.

Kenan K, Mack K, Paulozzi L . Trends in prescriptions for oxycodone and other commonly used opioids in the United States, 2000-2010. Open Med. 2013; 6(2):e41-7. PMC: 3659213. View

18.

Chiariello R, McCarthy C, Glaeser B, Shah A, Budde M, Stemper B . Chronicity of repeated blast traumatic brain injury associated increase in oxycodone seeking in rats. Behav Brain Res. 2022; 438:114181. PMC: 9993345. DOI: 10.1016/j.bbr.2022.114181. View

19.

Zhou L, Pruitt C, Shin C, Garcia A, Zavala A, See R . Fos expression induced by cocaine-conditioned cues in male and female rats. Brain Struct Funct. 2013; 219(5):1831-40. PMC: 3877704. DOI: 10.1007/s00429-013-0605-8. View

20.

Berardo L, Fabio M, Pautassi R . Post-weaning Environmental Enrichment, But Not Chronic Maternal Isolation, Enhanced Ethanol Intake during Periadolescence and Early Adulthood. Front Behav Neurosci. 2016; 10:195. PMC: 5061821. DOI: 10.3389/fnbeh.2016.00195. View