Decreased sensitivity in adolescent versus adult rats to the antidepressant-like effects of cannabidiol

Abstract

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.

Cannabidiol: A Potential New Alternative for the Treatment of Anxiety, Depression, and Psychotic Disorders

“…The administration of CBD displayed antidepressant-like effects at different doses in adolescents and adult male Sprague-Dawley rats [122]. The long-lasting effects of CBD were different: 2 days for adolescent and 21 days for adult rats.…”

Adolescent cocaine induced persistent negative affect in female rats exposed to early-life stress

“…The second part of the study evaluated the impact of adolescent cocaine exposure on affective-like behavior when the combination of several risk factors was present (i.e., female rats and early-life stress). The goal of the study was to ascertain the impact of cocaine exposure only in female rats (e.g., Rowson et al 2018 ) exposed to early-life stress, as opposed to perform a direct comparison with male rats and/or with non-stressed control rats, since prior similar studies have been done exclusively in male rats (Bis-Humbert et al 2020 ; 2021a , 2021b ), and we tackled the comparison with non-stressed controls in the first part of this study. At the behavioral level, the results showed that cocaine exposure did not alter affective-like behavior during adolescence, since no changes were observed in the forced swim, novelty-suppressed feeding, or sucrose preference tests.…”

“…Rats were screened in several behavioral tests performed consecutively across time to measure affective-like responses (Gururajan et al 2019 ) and as done in several prior studies (García-Cabrerizo and García-Fuster 2019 ; Jiménez-Romero et al 2020 ; Bis-Humbert et al 2020 ; 2021a , 2021b ): forced swim, open field, novelty-suppressed feeding, and sucrose preference (Fig. 1 ).…”

“…The overall number of Ki-67 + cells was quantified in the dentate gyrus of all sections (blindly to the experimental conditions) with a Leica DMR light microscope (63 × objective lens) by a modified unbiased procedure (Malberg et al, 2000 ; Malberg and Duman, 2003 ). This method counts every 8th section throughout the entire extent of the hippocampal dentate gyrus (i.e., Ki-67 + cells were located in the subgranular zone) to ensure an accurate count of individual cells and later multiplies that number by the sampling factor 8 to provide an estimate number of Ki-67 + cells per rat (see more details in our prior publications: García-Fuster et al 2010 , 2011 ; García-Fuster et al 2017; García-Cabrerizo and García-Fuster 2019 ; García-Cabrerizo et al 2020 ; Bis-Humbert et al 2020 , 2021b ).…”

Cannabidiol (CBD) in Cancer Management

“…Preclinical evidence indicates that CBD may reduce depressive-like behaviours, via several potential mechanisms of action (see [ 9 ]). Several animal studies have shown that CBD can reduce autonomic indices of stress and depression- and anxiety-like behaviours [ 128 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 ]. In terms of human studies, there are some published case studies which indicate that CBD reduced depressive symptoms [ 158 , 159 ] but no RCTs published in this area yet.…”