Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol
Psychopharmacology. 2020-02-21; 237(6): 1621-1631
DOI: 10.1007/s00213-020-05481-4
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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, Cra. de Valldemossa km 7.5,
E-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, Cra. de Valldemossa km 7.5,
E-07122, Palma, Spain. .
(5)Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
.
RATIONALE: Cannabidiol is a non-psychoactive phytocannabinoid with great
therapeutic potential in diverse psychiatric disorders; however, its
antidepressant potential has been mainly ascertained in adult rats.
OBJECTIVES: To compare the antidepressant-like response induced by cannabidiol
in adolescent and adult rats and the possible parallel modulation of hippocampal
neurogenesis.
METHODS: Male Sprague-Dawley rats were repeatedly treated with cannabidiol (3,
10, and 30 mg/kg) or vehicle (1 mL/kg) during adolescence (postnatal days, PND
27-33) or adulthood (PND 141-147) and exposed to 3 consecutive tests (forced
swim, open field, two-bottle choice) that quantified behavioral despair,
anxiety, and sucrose intake respectively.
RESULTS: Cannabidiol induced differential effects depending on the age and dose
administered, with a decreased sensitivity observed in adolescent rats: (1)
cannabidiol (30 mg/kg) decreased body weight only in adult rats; (2) cannabidiol
ameliorated behavioral despair in adolescent and adult rats, but with a
different dose sensitivity (10 vs. 30 mg/kg), and with a different extent (2 vs.
21 days post-treatment); (3) cannabidiol did not modulate anxiety-like behavior
at any dose tested in adolescent or adult rats; and (4) cannabidiol increased
sucrose intake in adult rats.
CONCLUSIONS: Our findings support the notion that cannabidiol exerts
antidepressant- and anorexigenic-like effects in adult rats and demonstrate a
decreased potential when administered in adolescent rats. Moreover, since
cannabidiol did not modulate hippocampal neurogenesis (cell proliferation and
early neuronal survival) in adolescent or adult rats, the results revealed
potential antidepressant-like effects induced by cannabidiol without the need of
regulating hippocampal neurogenesis.
DOI: 10.1007/s00213-020-05481-4
PMID: 32086540 [Indexed for MEDLINE]