Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats
Background: Cannabidiol (CBD) has received attention for the treatment of substance use disorders. In preclinical models of relapse, CBD attenuates drug seeking across several drugs of abuse, including cocaine. However, in these models CBD has not been consistently effective. This inconsistency in C...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Biological Psychiatry Global Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174321000604 |
| _version_ | 1828138149942919168 |
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| author | Hermina Nedelescu Grant E. Wagner Genna L. De Ness Ayla Carroll Tony M. Kerr Jingjun Wang Saiwen Zhang Stephen Chang Amy H. Than Nora E. Emerson Nobuyoshi Suto Friedbert Weiss |
| author_facet | Hermina Nedelescu Grant E. Wagner Genna L. De Ness Ayla Carroll Tony M. Kerr Jingjun Wang Saiwen Zhang Stephen Chang Amy H. Than Nora E. Emerson Nobuyoshi Suto Friedbert Weiss |
| author_sort | Hermina Nedelescu |
| collection | DOAJ |
| description | Background: Cannabidiol (CBD) has received attention for the treatment of substance use disorders. In preclinical models of relapse, CBD attenuates drug seeking across several drugs of abuse, including cocaine. However, in these models CBD has not been consistently effective. This inconsistency in CBD effects may be related to presently insufficient information on the full spectrum of CBD dose effects on drug-related behaviors. Methods: We address this issue by establishing a full dose-response profile of CBD’s actions using expression of cocaine-induced conditioned place preference as a model for drug-motivated behavior in male rats and by concurrently identifying dose-dependent effects of CBD on underlying neuronal activation and distinct neuronal phenotypes showing dose-dependent activation changes. Additionally, we established CBD levels in plasma and brain samples. Results: CBD produced linear increases in CBD brain/plasma concentrations but suppressed conditioned place preference in a distinct U-shaped manner. In parallel with its behavioral effects, CBD produced U-shaped suppressant effects on neuronal activation in the prelimbic but not infralimbic cortex or nucleus accumbens core and shell. RNAscope in situ hybridization identified suppression of glutamatergic and GABAergic (gamma-aminobutyric acidergic) signaling in the prelimbic cortex as a possible cellular mechanism for the attenuation of cocaine-induced conditioned place preference by CBD. Conclusions: The findings extend previous evidence on the potential of CBD in preventing drug-motivated behavior. However, CBD’s dose-response profile may have important dosing implications for future clinical applications and may contribute to the understanding of discrepant CBD effects on drug seeking reported in the literature. |
| first_indexed | 2024-04-11T18:31:31Z |
| format | Article |
| id | doaj.art-f01fa3d47cab4d19866f17697135a273 |
| institution | Directory Open Access Journal |
| issn | 2667-1743 |
| language | English |
| last_indexed | 2024-04-11T18:31:31Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj.art-f01fa3d47cab4d19866f17697135a2732022-12-22T04:09:26ZengElsevierBiological Psychiatry Global Open Science2667-17432022-01-01217078Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male RatsHermina Nedelescu0Grant E. Wagner1Genna L. De Ness2Ayla Carroll3Tony M. Kerr4Jingjun Wang5Saiwen Zhang6Stephen Chang7Amy H. Than8Nora E. Emerson9Nobuyoshi Suto10Friedbert Weiss11Department of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, CaliforniaDepartment of Neuroscience, The Scripps Research Institute, La Jolla, California; Nobuyoshi Suto, Ph.D.Department of Neuroscience, The Scripps Research Institute, La Jolla, California; Address correspondence to Friedbert Weiss, Ph.D.Background: Cannabidiol (CBD) has received attention for the treatment of substance use disorders. In preclinical models of relapse, CBD attenuates drug seeking across several drugs of abuse, including cocaine. However, in these models CBD has not been consistently effective. This inconsistency in CBD effects may be related to presently insufficient information on the full spectrum of CBD dose effects on drug-related behaviors. Methods: We address this issue by establishing a full dose-response profile of CBD’s actions using expression of cocaine-induced conditioned place preference as a model for drug-motivated behavior in male rats and by concurrently identifying dose-dependent effects of CBD on underlying neuronal activation and distinct neuronal phenotypes showing dose-dependent activation changes. Additionally, we established CBD levels in plasma and brain samples. Results: CBD produced linear increases in CBD brain/plasma concentrations but suppressed conditioned place preference in a distinct U-shaped manner. In parallel with its behavioral effects, CBD produced U-shaped suppressant effects on neuronal activation in the prelimbic but not infralimbic cortex or nucleus accumbens core and shell. RNAscope in situ hybridization identified suppression of glutamatergic and GABAergic (gamma-aminobutyric acidergic) signaling in the prelimbic cortex as a possible cellular mechanism for the attenuation of cocaine-induced conditioned place preference by CBD. Conclusions: The findings extend previous evidence on the potential of CBD in preventing drug-motivated behavior. However, CBD’s dose-response profile may have important dosing implications for future clinical applications and may contribute to the understanding of discrepant CBD effects on drug seeking reported in the literature.http://www.sciencedirect.com/science/article/pii/S2667174321000604CannabidiolCocaineConditioned place preferenceDose-responseU-ShapeRNAscope |
| spellingShingle | Hermina Nedelescu Grant E. Wagner Genna L. De Ness Ayla Carroll Tony M. Kerr Jingjun Wang Saiwen Zhang Stephen Chang Amy H. Than Nora E. Emerson Nobuyoshi Suto Friedbert Weiss Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats Biological Psychiatry Global Open Science Cannabidiol Cocaine Conditioned place preference Dose-response U-Shape RNAscope |
| title | Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats |
| title_full | Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats |
| title_fullStr | Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats |
| title_full_unstemmed | Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats |
| title_short | Cannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats |
| title_sort | cannabidiol produces distinct u shaped dose response effects on cocaine induced conditioned place preference and associated recruitment of prelimbic neurons in male rats |
| topic | Cannabidiol Cocaine Conditioned place preference Dose-response U-Shape RNAscope |
| url | http://www.sciencedirect.com/science/article/pii/S2667174321000604 |
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