Antidepressant-like effects of cannabidiol in a rat model of early-life stress with or without adolescent cocaine exposure
Tóm tắt
Further studies are needed to better understand the effects of potential novel antidepressants, such as cannabidiol, for the treatment of psychiatric disorders during adolescence. In this context, we evaluated in a rodent model of early-life stress (a single 24-h episode of maternal deprivation, PND 9), the antidepressant-like effects of adolescent cannabidiol alone and/or in combination with adolescent cocaine exposure (given the described beneficial effects of cannabidiol on reducing cocaine effects). Maternally deprived Sprague-Dawley male rats were treated in adolescence with cannabidiol (with or without concomitant cocaine) and exposed to a battery of behavioral tests (forced-swim, novelty-suppressed feeding, open field, sucrose preference) across time. Putative enduring molecular correlates (CB receptors, BDNF) were evaluated in the hippocampus by western blot. Cannabidiol exerted antidepressant- and anxiolytic-like effects in rats exposed to early-life stress. Cocaine did not alter affective-like behavior during adolescence in rats exposed to early-life stress; however, a depressive- and anxiogenic-like phenotype emerged during adulthood, and cannabidiol exerted some behavioral improvements, along with the growing literature supporting its beneficial role for reducing cocaine intake and/or reinstatement in rodents. Finally, cannabidiol did not modulate hippocampal CB receptors or BDNF proteins, and although the data raised interesting questions about the possible role of CB1 receptors on modulating the long-term effects of cocaine, future research is needed to expand these findings. Cannabidiol showed a promising therapeutic response in terms of ameliorating affect in a rat model of early-life stress during adolescence and up to adulthood.
Tài liệu tham khảo
Pisanti S, Malfitano AM, Ciaglia E, Lamberti A, Ranieri R, Cuomo G, et al. Cannabidiol: state of the art and new challenges for therapeutic applications. Pharmacol Ther. 2017;175:133–50.
Fernández-Ruiz J, Galve-Roperh I, Sagredo O, Guzmán M. Possible therapeutic applications of cannabis in the neuropsychopharmacology field. Eur Neuropsychopharmacol. 2020;36:217–34.
Sarris J, Sinclair J, Karamacoska D, Davidson M, Firth J. Medicinal cannabis for psychiatric disorders: a clinically-focused systematic review. BMC Psychiatry. 2020;20:24.
García-Gutiérrez MS, Navarrete F, Gasparyan A, Austrich-Olivares A, Sala F, Manzanares J. Cannabidiol: a potential new alternative for the treatment of anxiety, depression, and psychotic disorders. Biomolecules. 2020;10:1575.
Cipriani A, Zhou X, Del Giovane C, Hetrick SE, Qin B, Whittington C, et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis. Lancet. 2016;388:881–90.
Bis-Humbert C, García-Cabrerizo R, García-Fuster MJ. Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol. Psychopharmacology. 2020;237:1621–31.
García-Cabrerizo R, Ledesma-Corvi S, Bis-Humbert C, García-Fuster MJ. Sex differences in the antidepressant-like potential of repeated electroconvulsive seizures in adolescent and adult rats: Regulation of the early stages of hippocampal neurogenesis. Eur Neuropsychopharmacol. 2020;41:132–45.
Bis-Humbert C, García-Cabrerizo R, García-Fuster MJ. Increased negative affect when combining early-life maternal deprivation with adolescent, but not adult, cocaine exposure in male rats: regulation of hippocampal FADD. Psychopharmacology. 2021;238:411–20.
Weiss F, Gonzalez-Cuevas G. Unique treatment potential of cannabidiol for the prevention of relapse to drug use. Neuropsychopharmacology. 2019;44:229.
Gasparyan A, Navarrete F, Rodríguez-Arias M, Miñarro J, Manzanares J. Cannabidiol modulates behavioural and gene expression alterations induced by spontaneous cocaine withdrawal. Neurotherapeutics. 2020. https://doi.org/10.1007/s13311-020-00976-6.
Calpe-López C, Gasparyan A, Navarrete F, Manzanares J, Miñarro J, Aguilar MA. Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice. J Psychopharmacol. 2021. https://doi.org/10.1177/0269881120965952.
Campos AC, Fogaça MV, Sonego AB, Guimarães FS. Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol Res. 2016;112:119–27.
Luján MÁ, Castro-Zavala A, Alegre-Zurano L, Valverde O. Repeated cannabidiol treatment reduces cocaine intake and modulates neural proliferation and CB1R expression in the mouse hippocampus. Neuropharmacology. 2018;143:163–75.
Fogaça MV, Campos AC, Coelho LD, Duman RS, Guimãraes FS. The anxiolytic effects of cannabidiol in chronically stresses mice are mediated by the endocannabinoid system: role of neurogenesis and dendritic remodeling. Neuropharmacology. 2018;135:22–33.
García-Cabrerizo R, García-Fuster MJ. Opposite regulation of cannabinoid CB1 and CB2 receptors in the prefrontal cortex of rats treated with cocaine during adolescence. Neurosci Lett. 2016;615:60–5.
Llorente-Berzal A, Assis MA, Rubino T, Zamberletti E, Marco EM, Parolaro D, et al. Sex-dependent changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of maternal deprivation and adolescent cocaine exposure. Pharmacol Res. 2013;74:23–33.
Sales AJ, Fogaça MV, Sartim AG, Pereira VS, Wegener G, Guimarães FS, et al. Cannabidiol induces rapid and sustained antidepressant-like effects through increased BDNF signaling and synaptogenesis in the prefrontal cortex. Mol Neurobiol. 2019;56:1070–81.
Casarotto PC, Girych M, Fred SM, Kovaleva V, Moliner R, Enkavi G, et al. Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell. 2021;184:1299–313.
du Sert NP, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The arrive guidelines 2.0: updated guidelines for reporting animal research. Br J Pharmacol. 2020;177:3617–24.
García-Cabrerizo R, García-Fuster MJ. Adolescent cocaine exposure enhanced negative affect following drug re-exposure in adult rats: attenuation of c-Fos activation. J Psychopharmacol. 2019;33:154–62.
García-Cabrerizo R, Keller B, García-Fuster MJ. Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: consequences of cocaine exposure during adolescence on behavioral despair in adulthood. Neuroscience. 2015;304:302–15.
García-Fuster MJ, Parsegian A, Watson SJ, Akil H, Flagel SB. Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats. Psychopharmacology. 2017;234:1293–305.
Silote GP, Sartim A, Sales A, Eskelund A, Guimarães FS, Wegener G, et al. Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms. J Chem Neuroanat. 2019;98:104–16.
García-Fuster MJ, Perez JA, Clinton SM, Watson SJ, Akil H. Impact of cocaine on adult hippocampal neurogenesis in an animal model of differential propensity to drug abuse. Eur J Neurosci. 2010;31:79–89.
Parsegian A, García-Fuster MJ, Watson SJ, Flagel SB, Akil H. Adolescent cocaine experience differentially augments psychomotor sensitization in adulthood and alters dopamine receptor and epigenetic profiles in the nucleus accumbens of selectively bred high- and low-responder rats. Paper presented at the Society for Neuroscience Annual Meeting. San Diego, California, USA, 12–16 Nov 2016
Gonzalez-Cuevas G, Martin-Fardon R, Kerr TM, Stouffer DG, Parsons LH, Hammell DC, et al. Unique treatment potential of cannabidiol for the prevention of relapse to drug use: preclinical proof of principle. Neuropsychopharmacology. 2018;43:2036–45.
Mongeau-Pérusse V, Brissette S, Bruneau J, Conrod P, Dubreucq S, Gazil G, et al. Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: a randomized placebo-controlled trial. Addiction. 2021. https://doi.org/10.1111/add.15417.
Filip M, Faron-Górecka A, Kuśmider M, Gołda A, Frankowska M, Dziedzicka-Wasylewska M. Alterations in BDNF and trkB mRNAs following acute or sensitizing cocaine treatments and withdrawal. Brain Res. 2006;1071:218–25.