Antidepressant-like effects of cannabidiol in a rat model of early-life stress with or without adolescent cocaine exposure
Pharmacol. Rep. 2021-06-02; 73(4): 1195-1202
DOI: 10.1007/s43440-021-00285-5
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Bis-Humbert C(1)(2), García-Cabrerizo R(1)(2)(3), García-Fuster MJ(4)(5).
Author information:
(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. .
(5)Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
.
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.
© 2021. Maj Institute of Pharmacology Polish Academy of Sciences.