Cristian Bis-Humbert1,2, Rubén García-Cabrerizo1,2,3, M Julia García-Fuster4,5. 1. IUNICS, University of the Balearic Islands, Ctra. de Valldemossa km 7.5, 07122, Palma, Spain. 2. Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain. 3. APC Microbiome Ireland, University College Cork, Cork, Ireland. 4. IUNICS, University of the Balearic Islands, Ctra. de Valldemossa km 7.5, 07122, Palma, Spain. j.garcia@uib.es. 5. Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain. j.garcia@uib.es.
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Ani Gasparyan; Francisco Navarrete; Marta Rodríguez-Arias; José Miñarro; Jorge Manzanares Journal: Neurotherapeutics Date: 2020-11-23 Impact factor: 7.620
Authors: Claudia Calpe-López; Ani Gasparyan; Francisco Navarrete; Jorge Manzanares; Jose Miñarro; Maria A Aguilar Journal: J Psychopharmacol Date: 2021-01-09 Impact factor: 4.153