Environmental enrichment reduces heroin seeking following incubation of craving in both male and female rats

Barrera, Eddy D.; Loughlin, Lacey; Greenberger, Stephen; Hachimine, Priscila; Ranaldi, Robert

doi:10.1016/j.drugalcdep.2021.108852

Cited by 10 publications

(6 citation statements)

References 57 publications

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“…It is possible that environmental enrichment more effectively alters heroin seeking compared to social housing. Indeed, for single-housed rats, there is evidence that environmental enrichment alone reduces cue-induced heroin seeking (Barrera et al, 2021; Galaj et al, 2016; Imperio et al, 2018), prevents heroin-conditioned place preference (Galaj et al, 2016), and decreases compulsive cocaine and heroin seeking (Ewing & Ranaldi, 2018; Peck et al, 2015). Alternatively, social housing may only have effects as an interaction between housing and environmental enrichment.…”

Section: Discussionmentioning

confidence: 99%

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats.

Nett¹,

LaLumiere²

2023

Behavioral Neuroscience

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Evidence suggests that single housing in rats acts as a chronic stressor, raising the possibilities that it contributes to measures of heroin craving and that pair housing ameliorates such measures. This study aimed to determine whether pair housing after heroin self-administration reduces the incubation of craving, extinction, and reinstatement of heroin seeking. Single-housed female and male Sprague-Dawley rats underwent daily 6-hr heroin self-administration, wherein active lever presses produced a heroin infusion paired with light/tone cues. One day after self-administration, rats underwent a baseline cued-seeking test wherein active lever presses only produced light/tone cues. Immediately following this cued-seeking test, rats were either pair-housed with weight- and sex-matched naïve rat or remained single-housed for the rest of the study. For 14 days, rats remained in their homecages, after which they underwent a cued-seeking test to assess the incubation of craving compared to their baseline test. Rats then underwent extinction sessions followed by cue-induced and heroin-primed reinstatements. The findings reveal that pair-housed rats did not differ from single-housed rats in terms of the incubation of craving, extinction, or reinstatement of heroin seeking. Additionally, the results did not reveal any evidence of sex-based differences in the study. The present work indicates that pair housing during the forced abstinence period does not alter measures of heroin craving/seeking. These findings suggest that the chronic stress of single housing specifically during forced abstinence does not contribute to the degree of such measures.

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Section: Discussionmentioning

confidence: 99%

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats.

Nett¹,

LaLumiere²

2023

Behavioral Neuroscience

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“…Growing evidence supports that certain drug- or alcohol-induced neuroadaptations within the mesocorticolimbic system can be prevented or reversed by environmental enrichment (EE), a behavioral intervention that provides physical, social, and/or sensory stimulation ( Solinas et al, 2010 ; Galaj et al, 2020a ; Marrero-Cristobal et al, 2022 ). Our group and others have shown that EE, when administered after cocaine or heroin IVSA, can significantly facilitate abstinence ( Peck et al, 2015 ; Ewing and Ranaldi, 2018 ; Barrera et al, 2023 ) and reduce reinstatement of drug seeking ( Thiel et al, 2010 ; Ranaldi et al, 2011 ; Galaj et al, 2016 ; Barrera et al, 2021 ; He et al, 2022 ). Similarly, EE introduced after conditioning can reduce the expression or reinstatement of ethanol- ( Li et al, 2015 ), heroin- ( Galaj et al, 2016 ), and cocaine- ( Solinas et al, 2008 ; Chauvet et al, 2009 ) conditioned place preference.…”

Section: Introductionmentioning

confidence: 77%

“…Perhaps, 15 days of EE is not sufficient to restore CRF1 signaling. We previously found behavioral effects of EE when implemented for 15 ( Barrera et al, 2021 ), 30 ( Galaj et al, 2016 ), or 60 days ( Galaj et al, 2017 ). But based on the current findings, it appears that 15 days is not sufficient to restore the CRF system after chronic opioid IVSA.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression

Galaj,

Barrera,

Persaud

et al. 2023

International Journal of Neuropsychopharmacology

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Background There is a strong link between chronic stress and vulnerability to drug abuse and addiction. Corticotropin releasing factor (CRF) is central to the stress response that contributes to continuation and relapse to heroin abuse. Chronic heroin exposure can exacerbate CRF production, leading to dysregulation of the midbrain CRF-dopamine-glutamate interaction Methods and Results Here we investigated the role of midbrain CRF 1 receptors in heroin self-administration and assessed neuroplasticity in CRF1 receptor expression in key opioid addiction brain regions. Infusions of antalarmin (a CRF1 receptor antagonist) into the ventral tegmental area (VTA) dose-dependently reduced heroin self-administration in rats but had no impact on food reinforcement or locomotor activity in rats. Using RNAscope in-situ hybridization, we found that heroin, but not saline, self-administration upregulated CRF1 receptor mRNA in the VTA, particularly on dopamine neurons. AMPA GluR1 and DAT mRNA in VTA neurons were not impacted by heroin. The Western Blot assay showed that CRF1 receptors were upregulated in the VTA and nucleus accumbens. No significant changes in CRF1 protein expression were detected in the prefrontal cortex, insula, dorsal hippocampus and substantia nigra. In addition, we found that 15 days of environmental enrichment implemented after heroin self-administration does not reverse upregulation of VTA CRF1 receptor mRNA but it downregulates dopamine transporter mRNA Conclusions Overall, these data suggest that heroin self-administration requires stimulation of VTA CRF1 receptors and upregulates their expression in brain regions involved in reinforcement. Such long-lasting neuroadaptations may contribute to continuation of drug use and relapse due to stress exposure and are not easily reversed by EE exposure.

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“…It is possible that environmental enrichment more effectively alters heroin seeking compared to social housing. Indeed, for single-housed rats, there is evidence that environmental enrichment alone reduces cue-induced heroin seeking (Galaj et al, 2016; Imperio et al, 2018; Barrera et al, 2021), prevents heroin conditioned place preference (Galaj et al, 2016), and decreases compulsive cocaine and heroin seeking (Peck et al, 2015; Ewing and Ranaldi, 2018). Alternatively, social housing may only have effects as an interaction between housing and environmental enrichment.…”

Section: Discussionmentioning

confidence: 99%

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats

Nett

LaLumiere

2022

Preprint

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Rationale: Evidence suggests that single housing in rats acts as a chronic stressor, raising the possibilities that it contributes to measures of heroin craving and that pair housing ameliorates such measures. Objectives: This study aimed to determine whether pair housing after heroin self-administration reduces the incubation of craving, extinction, and reinstatement of heroin seeking. Methods: Single-housed female and male Sprague-Dawley rats underwent daily 6-h heroin self-administration, wherein active lever presses produced a heroin infusion paired with light/tone cues. One d after self-administration, rats underwent a baseline cued-seeking test wherein active lever presses only produced light/tone cues. Immediately following this cued-seeking test, rats were either pair-housed with a weight- and sex-matched naive rat or remained single-housed for the rest of the study. For 14 d, rats remained in their homecages, after which they underwent a cued-seeking test to assess the incubation of craving compared to their baseline test. Rats then underwent extinction sessions followed by cue-induced and heroin-primed reinstatements. Results: The findings reveal that pair-housed rats did not differ from single-housed rats in terms of the incubation of craving, extinction, or reinstatement of heroin seeking. Additionally, the results did not reveal any evidence of sex-based differences in the study. Conclusions: The present work indicates that pair housing during the forced abstinence period does not alter measures of heroin craving/seeking. These findings suggest that the chronic stress of single housing specifically during forced abstinence does not contribute to the degree of such measures.

show abstract

Environmental enrichment reduces heroin seeking following incubation of craving in both male and female rats

Cited by 10 publications

References 57 publications

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats.

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats.

The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression

Pair housing does not alter incubation of craving, extinction, and reinstatement after heroin self-administration in female and male rats

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