Oxytocin attenuates demand for cocaine in female rats
There are substantial sex differences in substance use disorders (SUDs), and a key feature of SUD is pathologically high economic demand for drug. The hypothalamic neuropeptide oxytocin (OXT) is heavily implicated in the modern treatment of SUDs. Using a within-session threshold behavioral economics...
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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/S2772392525000033 |
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| author | Amy S. Kohtz Hannah Davies Belle Lin Gary Aston-Jones |
| author_facet | Amy S. Kohtz Hannah Davies Belle Lin Gary Aston-Jones |
| author_sort | Amy S. Kohtz |
| collection | DOAJ |
| description | There are substantial sex differences in substance use disorders (SUDs), and a key feature of SUD is pathologically high economic demand for drug. The hypothalamic neuropeptide oxytocin (OXT) is heavily implicated in the modern treatment of SUDs. Using a within-session threshold behavioral economics (BE) procedure, we quantified demand elasticity (a, inverse motivation) and free consumption (Q0) in male and female rats to investigate the effect of OXT on cocaine demand. Results showed that OXT decreased motivation for cocaine; an effect greater during the high-demand phase (diestrus, low progesterone, P4) vs low demand phases (proestrus, high P4). We confirmed our prior findings that P4 attenuates cocaine demand in female rats and that chronic cocaine self-administration disrupts estrus cyclicity. Following each injection, OXT at either 0.1mg/kg or 0.3mg/kg restored estrous cycling in intact females with prior cocaine experience for one week and remained effective with up to 4 weeks of injections. Fos reactivity in OXT+ neurons was greater when rats were in proestrus compared to diestrus and significantly correlated to motivation and circulating levels of P4. Finally, using ovariectomized females with P4 replacement, we show that P4’s demand attenuating effects are reversed by atosiban (1.0 mg/kg, IP), an OXT antagonist. These data show an interaction between oxytocin and progesterone in female rats that may underlie differences in cocaine demand between sexes. Additionally, we show critical periods for using OXT as a treatment to reduce cocaine demand in females. Our results indicate novel therapeutic treatments for SUDs must be tailored to hormonal states. |
| format | Article |
| id | doaj-art-5f065e82ae76461a85db97d513877f4e |
| institution | Kabale University |
| issn | 2772-3925 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Addiction Neuroscience |
| spelling | doaj-art-5f065e82ae76461a85db97d513877f4e2025-01-23T05:27:59ZengElsevierAddiction Neuroscience2772-39252025-06-0115100197Oxytocin attenuates demand for cocaine in female ratsAmy S. Kohtz0Hannah Davies1Belle Lin2Gary Aston-Jones3Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA; Corresponding author.Brain Health Institute, Rutgers University, Piscataway, NJ 08854, USABrain Health Institute, Rutgers University, Piscataway, NJ 08854, USABrain Health Institute, Rutgers University, Piscataway, NJ 08854, USAThere are substantial sex differences in substance use disorders (SUDs), and a key feature of SUD is pathologically high economic demand for drug. The hypothalamic neuropeptide oxytocin (OXT) is heavily implicated in the modern treatment of SUDs. Using a within-session threshold behavioral economics (BE) procedure, we quantified demand elasticity (a, inverse motivation) and free consumption (Q0) in male and female rats to investigate the effect of OXT on cocaine demand. Results showed that OXT decreased motivation for cocaine; an effect greater during the high-demand phase (diestrus, low progesterone, P4) vs low demand phases (proestrus, high P4). We confirmed our prior findings that P4 attenuates cocaine demand in female rats and that chronic cocaine self-administration disrupts estrus cyclicity. Following each injection, OXT at either 0.1mg/kg or 0.3mg/kg restored estrous cycling in intact females with prior cocaine experience for one week and remained effective with up to 4 weeks of injections. Fos reactivity in OXT+ neurons was greater when rats were in proestrus compared to diestrus and significantly correlated to motivation and circulating levels of P4. Finally, using ovariectomized females with P4 replacement, we show that P4’s demand attenuating effects are reversed by atosiban (1.0 mg/kg, IP), an OXT antagonist. These data show an interaction between oxytocin and progesterone in female rats that may underlie differences in cocaine demand between sexes. Additionally, we show critical periods for using OXT as a treatment to reduce cocaine demand in females. Our results indicate novel therapeutic treatments for SUDs must be tailored to hormonal states.http://www.sciencedirect.com/science/article/pii/S2772392525000033Sex differencesOxytocinBehavioral economicsProgesteroneCocaine |
| spellingShingle | Amy S. Kohtz Hannah Davies Belle Lin Gary Aston-Jones Oxytocin attenuates demand for cocaine in female rats Addiction Neuroscience Sex differences Oxytocin Behavioral economics Progesterone Cocaine |
| title | Oxytocin attenuates demand for cocaine in female rats |
| title_full | Oxytocin attenuates demand for cocaine in female rats |
| title_fullStr | Oxytocin attenuates demand for cocaine in female rats |
| title_full_unstemmed | Oxytocin attenuates demand for cocaine in female rats |
| title_short | Oxytocin attenuates demand for cocaine in female rats |
| title_sort | oxytocin attenuates demand for cocaine in female rats |
| topic | Sex differences Oxytocin Behavioral economics Progesterone Cocaine |
| url | http://www.sciencedirect.com/science/article/pii/S2772392525000033 |
| work_keys_str_mv | AT amyskohtz oxytocinattenuatesdemandforcocaineinfemalerats AT hannahdavies oxytocinattenuatesdemandforcocaineinfemalerats AT bellelin oxytocinattenuatesdemandforcocaineinfemalerats AT garyastonjones oxytocinattenuatesdemandforcocaineinfemalerats |