Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats
Post-traumatic stress disorder (PTSD) develops in a sub-population of people exposed to trauma and is highly comorbid with opioid use disorder (OUD). The neurobiology of comorbid PTSD+OUD, especially with respect to sex differences, is poorly understood. Here we investigated the sex-specific effects...
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| Language: | English |
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Elsevier
2025-06-01
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| Series: | Addiction Neuroscience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772392525000161 |
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| author | Courtney S. Wilkinson Siya Bhutani Wonn Pyon Marek Schwendt Lori A. Knackstedt |
| author_facet | Courtney S. Wilkinson Siya Bhutani Wonn Pyon Marek Schwendt Lori A. Knackstedt |
| author_sort | Courtney S. Wilkinson |
| collection | DOAJ |
| description | Post-traumatic stress disorder (PTSD) develops in a sub-population of people exposed to trauma and is highly comorbid with opioid use disorder (OUD). The neurobiology of comorbid PTSD+OUD, especially with respect to sex differences, is poorly understood. Here we investigated the sex-specific effects of predator scent stress on intravenous (IV) oxycodone self-administration (SA), cue-primed reinstatement, and pre- and post-stress corticosterone (CORT) concentrations. Upon detecting effects of stress on oxycodone IVSA, the nucleus accumbens (NA) dopamine response to oxycodone was assessed. Male and female rats received a single 10-minute exposure to the predator scent TMT or the control condition. One week later, rats were tested for anxiety-like behavior on the elevated plus maze and underwent oxycodone IVSA, instrumental extinction, and a cue-primed reinstatement test. In a separate cohort of only female rats, the NA core dopamine response to IV oxycodone (0, 0.25, 0.5 mg/kg) was assessed using fiber photometry. TMT increased anxiety-like behavior one week later in male and female rats. Baseline CORT was negatively correlated with anxiety-like behavior in males. TMT exposure reduced oxycodone intake exclusively in females, with no effects on instrumental extinction or cue-primed reinstatement in either sex. Female rats demonstrated a dose-dependent increase in NA core dopamine signal following oxycodone administration that was blunted by a history of TMT exposure. These results indicate that TMT exposure diminishes the NA core dopamine response to oxycodone in females, reducing oxycodone IVSA. These results are consistent with stress-induced reward insensitivity that has been observed following stress in both rodents and humans. |
| format | Article |
| id | doaj-art-ca479fdd7ff9497ebe15cb969474ea77 |
| institution | OA Journals |
| issn | 2772-3925 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Addiction Neuroscience |
| spelling | doaj-art-ca479fdd7ff9497ebe15cb969474ea772025-08-20T01:56:32ZengElsevierAddiction Neuroscience2772-39252025-06-011510021010.1016/j.addicn.2025.100210Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female ratsCourtney S. Wilkinson0Siya Bhutani1Wonn Pyon2Marek Schwendt3Lori A. Knackstedt4Psychology Department, 945 Center Drive, University of Florida, Gainesville, FL, USA; Center for Addiction Research and Education, 1395 Center Dr, Suite D2-013, University of Florida, Gainesville, FL, USA; Corresponding author at: 945 Center Drive, Psychology Department, Gainesville, FL 32611.Psychology Department, 945 Center Drive, University of Florida, Gainesville, FL, USACenter for Addiction Research and Education, 1395 Center Dr, Suite D2-013, University of Florida, Gainesville, FL, USA; Department of Neuroscience, 1149 Newell Drive, University of Florida, Gainesville, FL, USAPsychology Department, 945 Center Drive, University of Florida, Gainesville, FL, USA; Center for Addiction Research and Education, 1395 Center Dr, Suite D2-013, University of Florida, Gainesville, FL, USAPsychology Department, 945 Center Drive, University of Florida, Gainesville, FL, USA; Center for Addiction Research and Education, 1395 Center Dr, Suite D2-013, University of Florida, Gainesville, FL, USAPost-traumatic stress disorder (PTSD) develops in a sub-population of people exposed to trauma and is highly comorbid with opioid use disorder (OUD). The neurobiology of comorbid PTSD+OUD, especially with respect to sex differences, is poorly understood. Here we investigated the sex-specific effects of predator scent stress on intravenous (IV) oxycodone self-administration (SA), cue-primed reinstatement, and pre- and post-stress corticosterone (CORT) concentrations. Upon detecting effects of stress on oxycodone IVSA, the nucleus accumbens (NA) dopamine response to oxycodone was assessed. Male and female rats received a single 10-minute exposure to the predator scent TMT or the control condition. One week later, rats were tested for anxiety-like behavior on the elevated plus maze and underwent oxycodone IVSA, instrumental extinction, and a cue-primed reinstatement test. In a separate cohort of only female rats, the NA core dopamine response to IV oxycodone (0, 0.25, 0.5 mg/kg) was assessed using fiber photometry. TMT increased anxiety-like behavior one week later in male and female rats. Baseline CORT was negatively correlated with anxiety-like behavior in males. TMT exposure reduced oxycodone intake exclusively in females, with no effects on instrumental extinction or cue-primed reinstatement in either sex. Female rats demonstrated a dose-dependent increase in NA core dopamine signal following oxycodone administration that was blunted by a history of TMT exposure. These results indicate that TMT exposure diminishes the NA core dopamine response to oxycodone in females, reducing oxycodone IVSA. These results are consistent with stress-induced reward insensitivity that has been observed following stress in both rodents and humans.http://www.sciencedirect.com/science/article/pii/S2772392525000161AnhedoniaSubstance use disorderAddictionRelapse |
| spellingShingle | Courtney S. Wilkinson Siya Bhutani Wonn Pyon Marek Schwendt Lori A. Knackstedt Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats Addiction Neuroscience Anhedonia Substance use disorder Addiction Relapse |
| title | Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats |
| title_full | Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats |
| title_fullStr | Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats |
| title_full_unstemmed | Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats |
| title_short | Predator scent stress reduces oxycodone self-administration and the nucleus accumbens dopamine response to oxycodone in female rats |
| title_sort | predator scent stress reduces oxycodone self administration and the nucleus accumbens dopamine response to oxycodone in female rats |
| topic | Anhedonia Substance use disorder Addiction Relapse |
| url | http://www.sciencedirect.com/science/article/pii/S2772392525000161 |
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