The effects of strain and estrous cycle on heroin- and sugar-maintained responding in female rats

Schmidt, Karl T.; Sharp, Jessica L.; Ethridge, Sarah B.; Pearson, Tallia; Ballard, Shannon; Potter, Kenzie M.; Smith, Mark A.

doi:10.1016/j.bbr.2021.113329

Cited by 9 publications

(8 citation statements)

References 19 publications

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“…3 G and K ). In addition, there are some potential differences in heroin-primed reinstatement levels between Long Evans and the Sprague-Dawley rats, consistent with known strain effects in rodent self-administration studies ( 17 , 18 ). However, in our studies we did not directly compare strains within the same experiment, so we cannot draw firm conclusions based on our findings reported here.…”

Section: Resultssupporting

confidence: 64%

Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner

Anderson

Tsvetkov

Galante

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Opioid use produces enduring associations between drug reinforcement/euphoria and discreet or diffuse cues in the drug-taking environment. These powerful associations can trigger relapse in individuals recovering from opioid use disorder (OUD). Here, we sought to determine whether the epigenetic enzyme, histone deacetylase 5 (HDAC5), regulates relapse-associated behavior in an animal model of OUD. We examined the effects of nucleus accumbens (NAc) HDAC5 on both heroin- and sucrose-seeking behaviors using operant self-administration paradigms. We utilized cre-dependent viral-mediated approaches to investigate the cell-type–specific effects of HDAC5 on heroin-seeking behavior, gene expression, and medium spiny neuron (MSN) cell and synaptic physiology. We found that NAc HDAC5 functions during the acquisition phase of heroin self-administration to limit future relapse-associated behavior. Moreover, overexpressing HDAC5 in the NAc suppressed context-associated and reinstated heroin-seeking behaviors, but it did not alter sucrose seeking. We also found that HDAC5 functions within dopamine D1 receptor-expressing MSNs to suppress cue-induced heroin seeking, and within dopamine D2 receptor-expressing MSNs to suppress drug-primed heroin seeking. Assessing cell-type–specific transcriptomics, we found that HDAC5 reduced expression of multiple ion transport genes in both D1- and D2-MSNs. Consistent with this observation, HDAC5 also produced firing rate depression in both MSN classes. These findings revealed roles for HDAC5 during active heroin use in both D1- and D2-MSNs to limit distinct triggers of drug-seeking behavior. Together, our results suggest that HDAC5 might limit relapse vulnerability through regulation of ion channel gene expression and suppression of MSN firing rates during active heroin use.

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Section: Resultssupporting

confidence: 64%

Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner

Anderson

Tsvetkov

Galante

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…One recent study found that rats self-administered similar amounts of sucrose regardless of estrous cycle phase ( Schmidt et al, 2021 ). In this article, rats were also trained on heroin self-administration before sucrose self-administration, and there was an observed decrease in heroin taking during proestrus.…”

Section: Discussionmentioning

confidence: 99%

Opioid and Sucrose Craving Are Accompanied by Unique Behavioral and Affective Profiles after Extended Abstinence in Male and Female Rats

Mayberry

Desalvo

Bavley

et al. 2022

eNeuro

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“…Consistent with this, evidence suggests that when sex steroid receptors are relatively inactive due to low levels of estrogen and progesterone, there is an enhanced opioid intake. For example, heroin self-administration in female rats is highest during the nonproestrus phases of the ovarian cycle (Lacy et al, 2016; Schmidt et al, 2021), when levels of both estrogen and progesterone are relatively low. Conversely, heroin and remifentanil self-administration is reduced by administration of estrogen, but not by progesterone, indicating the estrogen receptor is critically involved (Sharp et al, 2021; Smith et al, 2020); however, also see (Roth et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

Bardo¹,

Chandler²,

Denehy³

et al. 2023

Experimental and Clinical Psychopharmacology

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There is comorbidity between posttraumatic stress disorder (PTSD) and opioid use disorder (OUD), perhaps because PTSD-like stressful experiences early in life alter the hypothalamic-pituitary-adrenal stress axis to increase the risk for OUD. The present study determined if the glucocorticoid receptor antagonist PT150 reduces the escalation of fentanyl intake in rats exposed to a "two-hit" model of early-life stress (isolation rearing and acute stress). Male and female rats were raised during adolescence in either isolated or social housing and then were given either a single acute stress (restraint and cold-water swim) or control treatment in young adulthood. Rats were then treated daily with PT150 (50 mg/kg, oral) or placebo and were tested for acquisition of fentanyl self-administration in 1-hr sessions, followed by escalation across 6-hr sessions. Regardless of PT150 treatment or sex, acquisition of fentanyl self-administration in 1-hr sessions was greater in isolate-housed rats compared to social-housed rats; the acute stress manipulation did not have an effect on self-administration even though it transiently increased plasma corticosterone levels. During the 6-hr sessions, escalation of fentanyl was observed across all treatment groups; however, there was a significant PT150 Treatment × Sex interaction. While males self-administered more than females overall, PT150 decreased intake in males and increased intake in females, thus negating the sex difference. Although PT150 may serve as an effective treatment for reducing the risk of OUD following early-life stress in males, further work is needed to determine the mechanism underlying the differential effects of PT150 in males and females. Public Health SignificanceThe effect of the glucocorticoid receptor antagonist PT150 on fentanyl self-administration in male and female rats subjected to early-life stress was examined. Males self-administered more than females, but PT150 eliminated this sex difference, with intake decreasing in males and increasing in females. PT150 may be useful to treat opioid use disorder in males, but not in females.

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The effects of strain and estrous cycle on heroin- and sugar-maintained responding in female rats

Cited by 9 publications

References 19 publications

Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner

Epigenetic function during heroin self-administration controls future relapse-associated behavior in a cell type-specific manner

Opioid and Sucrose Craving Are Accompanied by Unique Behavioral and Affective Profiles after Extended Abstinence in Male and Female Rats

Effect of the glucocorticoid receptor antagonist PT150 on acquisition and escalation of fentanyl self-administration following early-life stress.

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