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• W3092837885 endingPage "870" @default.
• W3092837885 startingPage "860" @default.
• W3092837885 abstract "Cocaine abuse continues to be a serious health problem worldwide. Despite intense research, there is still no FDA-approved medication to treat cocaine use disorder (CUD). In this report, we explored the potential utility of beta-caryophyllene (BCP), an FDA-approved food additive for the treatment of CUD. We found that BCP, when administered intraperitoneally or intragastrically, dose-dependently attenuated cocaine self-administration, cocaine-conditioned place preference, and cocaine-primed reinstatement of drug seeking in rats. In contrast, BCP failed to alter food self-administration or cocaine-induced hyperactivity. It also failed to maintain self-administration in a drug substitution test, suggesting that BCP has no abuse potential. BCP was previously reported to be a selective CB2 receptor agonist. Unexpectedly, pharmacological blockade or genetic deletion of CB1, CB2, or GPR55 receptors in gene-knockout mice failed to alter BCP’s action against cocaine self-administration, suggesting the involvement of non-CB1, non-CB2, and non-GPR55 receptor mechanisms. Furthermore, pharmacological blockade of μ opioid receptor or Toll-like receptors complex failed to alter, while blockade of peroxisome proliferator-activated receptors (PPARα, PPARγ) reversed BCP-induced reduction in cocaine self-administration, suggesting the involvement of PPARα and PPARγ in BCP’s action. Finally, we used electrical and optogenetic intracranial self-stimulation (eICSS, oICSS) paradigms to study the underlying neural substrate mechanisms. We found that BCP is more effective in attenuation of cocaine-enhanced oICSS than eICSS, the former driven by optical activation of midbrain dopamine neurons in DAT-cre mice. These findings indicate that BCP may be useful for the treatment of CUD, likely by stimulation of PPARα and PPARγ in the mesolimbic system." @default.
• W3092837885 created "2020-10-22" @default.
• W3092837885 creator A5006332988 @default.
• W3092837885 creator A5026940576 @default.
• W3092837885 creator A5035565515 @default.
• W3092837885 creator A5045379902 @default.
• W3092837885 creator A5060050668 @default.
• W3092837885 creator A5071186087 @default.
• W3092837885 creator A5074339191 @default.
• W3092837885 date "2020-10-17" @default.
• W3092837885 modified "2023-10-18" @default.
• W3092837885 title "Beta-caryophyllene inhibits cocaine addiction-related behavior by activation of PPARα and PPARγ: repurposing a FDA-approved food additive for cocaine use disorder" @default.
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