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

青少年与成年大鼠对大麻二酚抗抑郁样作用的敏感性降低。

  • 影响因子:3.50
  • DOI:10.1007/s00213-020-05481-4
  • 作者列表:"Bis-Humbert C","García-Cabrerizo R","García-Fuster MJ
  • 发表时间:2020-02-21
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.

摘要

原理: 大麻二酚是一种非精神活性植物大麻素,在多种精神疾病中具有巨大的治疗潜力; 然而,其抗抑郁潜力主要在成年大鼠中确定。 目的: 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。 方法: 雄性 Sprague-Dawley 大鼠在青春期 (出生后第 27-33 天,PND) 重复使用大麻二酚 (3 、 10 和 30 mg/kg) 或溶剂 (1 mL/kg) 或成年 (PND 141-147) 和暴露于 3 个连续的测试 (强迫游泳,旷场,两瓶选择) 量化的行为绝望,分别为焦虑和蔗糖摄入。 结果: 大麻二酚诱导的不同效应取决于施用的年龄和剂量,在青春期大鼠中观察到敏感性降低 :( 1) 大麻二酚 (30 mg/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,但具有不同的剂量敏感性(10 vs. 30 mg/kg),并以不同程度 (2 vs。治疗后 21 天); (3) 大麻二酚不调节青少年或成年大鼠任何剂量的焦虑样行为; (4) 大麻二酚增加成年大鼠的蔗糖摄入。 结论: 我们的研究结果支持大麻二酚在成年大鼠中发挥抗抑郁和厌食样作用的观点,并证明在青春期大鼠中给药时潜力降低。此外,由于大麻二酚不调节青春期或成年大鼠的海马神经发生 (细胞增殖和早期神经元存活), 结果揭示了大麻二酚诱导的潜在抗抑郁样作用,而不需要调节海马神经发生。

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发表时间:2020-01-22
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影响因子:6.22
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