IUNICS, University of the Balearic Islands, Cra. de Valldemossa km 7.5, E-07122, Palma, Spain.
Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
Psychopharmacology (Berl). 2020 Jun;237(6):1621-1631. doi: 10.1007/s00213-020-05481-4. Epub 2020 Feb 21.
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.
To compare the antidepressant-like response induced by cannabidiol in adolescent and adult rats and the possible parallel modulation of hippocampal neurogenesis.
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.
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.
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.
大麻二酚是一种非精神活性植物大麻素，在多种精神疾病中有很大的治疗潜力；然而，其抗抑郁作用主要在成年大鼠中得到证实。
比较大麻二酚在青少年和成年大鼠中诱导的抗抑郁样反应，以及海马神经发生的可能平行调节。
雄性 Sprague-Dawley 大鼠在青春期（出生后第 27-33 天）或成年期（第 141-147 天）反复接受大麻二酚（3、10 和 30mg/kg）或载体（1mL/kg）治疗，并进行 3 项连续测试（强迫游泳、旷场、双瓶选择），分别量化行为绝望、焦虑和蔗糖摄入。
大麻二酚的作用取决于年龄和给药剂量，在青少年大鼠中观察到敏感性降低：（1）大麻二酚（30mg/kg）仅在成年大鼠中降低体重；（2）大麻二酚改善了青少年和成年大鼠的行为绝望，但剂量敏感性不同（10 与 30mg/kg），且治疗后持续时间不同（2 与 21 天）；（3）大麻二酚在任何测试剂量下均不调节青少年或成年大鼠的焦虑样行为；（4）大麻二酚增加了成年大鼠的蔗糖摄入量。
我们的发现支持大麻二酚在成年大鼠中表现出抗抑郁和厌食样作用的观点，并表明在青春期大鼠中作用潜力降低。此外，由于大麻二酚在青少年或成年大鼠中均不调节海马神经发生（细胞增殖和早期神经元存活），结果表明大麻二酚诱导的潜在抗抑郁样作用无需调节海马神经发生。
