N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice
Abstract The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (coc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-07-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02574-4 |
| _version_ | 1827875422300274688 |
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| author | Samah Shahen-Zoabi Reem Smoum Alexey Bingor Etty Grad Alina Nemirovski Tawfeeq Shekh-Ahmad Raphael Mechoulam Rami Yaka |
| author_facet | Samah Shahen-Zoabi Reem Smoum Alexey Bingor Etty Grad Alina Nemirovski Tawfeeq Shekh-Ahmad Raphael Mechoulam Rami Yaka |
| author_sort | Samah Shahen-Zoabi |
| collection | DOAJ |
| description | Abstract The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (cocaine) is involved in regulating the development and expression of cocaine-conditioned reward and sensitization. We therefore hypothesized that drug-induced elevation in endocannabinoids (eCBs) and/or eCB-like molecules (eCB-Ls) may represent a protective mechanism against drug insult, and boosting their levels exogenously may strengthen their neuroprotective effects. Here, we determine the involvement of ECS in alcohol addiction. We first measured the eCBs and eCB-Ls levels in different brain reward system regions following chronic alcohol self-administration using LC–MS. We have found that following chronic intermittent alcohol consumption, N-oleoyl glycine (OlGly) levels were significantly elevated in the prefrontal cortex (PFC), and N-oleoyl alanine (OlAla) was significantly elevated in the PFC, nucleus accumbens (NAc) and ventral tegmental area (VTA) in a region-specific manner. We next tested whether exogenous administration of OlGly or OlAla would attenuate alcohol consumption and preference. We found that systemic administration of OlGly or OlAla (60 mg/kg, intraperitoneal) during intermittent alcohol consumption significantly reduced alcohol intake and preference without affecting the hedonic state. These findings suggest that the ECS negatively regulates alcohol consumption and boosting selective eCBs exogenously has beneficial effects against alcohol consumption and potentially in preventing relapse. |
| first_indexed | 2024-03-12T17:06:35Z |
| format | Article |
| id | doaj.art-e5e1f249c9224f58a2b1879e70fd43fd |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-12T17:06:35Z |
| publishDate | 2023-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-e5e1f249c9224f58a2b1879e70fd43fd2023-08-06T11:25:30ZengNature Publishing GroupTranslational Psychiatry2158-31882023-07-011311810.1038/s41398-023-02574-4N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in miceSamah Shahen-Zoabi0Reem Smoum1Alexey Bingor2Etty Grad3Alina Nemirovski4Tawfeeq Shekh-Ahmad5Raphael Mechoulam6Rami Yaka7Institute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemInstitute for Drug Research (IDR), School of Pharmacy, Faculty of Medicine, The Hebrew University of JerusalemAbstract The endocannabinoid system (ECS) plays a key modulatory role during synaptic plasticity and homeostatic processes in the brain and has an important role in the neurobiological processes underlying drug addiction. We have previously shown that an elevated ECS response to psychostimulant (cocaine) is involved in regulating the development and expression of cocaine-conditioned reward and sensitization. We therefore hypothesized that drug-induced elevation in endocannabinoids (eCBs) and/or eCB-like molecules (eCB-Ls) may represent a protective mechanism against drug insult, and boosting their levels exogenously may strengthen their neuroprotective effects. Here, we determine the involvement of ECS in alcohol addiction. We first measured the eCBs and eCB-Ls levels in different brain reward system regions following chronic alcohol self-administration using LC–MS. We have found that following chronic intermittent alcohol consumption, N-oleoyl glycine (OlGly) levels were significantly elevated in the prefrontal cortex (PFC), and N-oleoyl alanine (OlAla) was significantly elevated in the PFC, nucleus accumbens (NAc) and ventral tegmental area (VTA) in a region-specific manner. We next tested whether exogenous administration of OlGly or OlAla would attenuate alcohol consumption and preference. We found that systemic administration of OlGly or OlAla (60 mg/kg, intraperitoneal) during intermittent alcohol consumption significantly reduced alcohol intake and preference without affecting the hedonic state. These findings suggest that the ECS negatively regulates alcohol consumption and boosting selective eCBs exogenously has beneficial effects against alcohol consumption and potentially in preventing relapse.https://doi.org/10.1038/s41398-023-02574-4 |
| spellingShingle | Samah Shahen-Zoabi Reem Smoum Alexey Bingor Etty Grad Alina Nemirovski Tawfeeq Shekh-Ahmad Raphael Mechoulam Rami Yaka N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice Translational Psychiatry |
| title | N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice |
| title_full | N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice |
| title_fullStr | N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice |
| title_full_unstemmed | N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice |
| title_short | N-oleoyl glycine and N-oleoyl alanine attenuate alcohol self-administration and preference in mice |
| title_sort | n oleoyl glycine and n oleoyl alanine attenuate alcohol self administration and preference in mice |
| url | https://doi.org/10.1038/s41398-023-02574-4 |
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