Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, 1033 Pine Avenue West, Montreal, Canada H3A1A1.
Neurobiol Dis. 2010 Mar;37(3):641-55. doi: 10.1016/j.nbd.2009.11.020. Epub 2009 Dec 5.
The pathophysiological neural mechanism underlying the depressogenic and anxiogenic effects of chronic adolescent cannabinoid use may be linked to perturbations in monoaminergic neurotransmission. We tested this hypothesis by administering the CB(1) receptor agonist WIN55,212-2, once daily for 20 days to adolescent and adult rats, subsequently subjecting them to tests for emotional reactivity paralleled by the in vivo extracellular recordings of serotonergic and noradrenergic neurons. Chronic adolescent exposure but not adult exposure to low (0.2 mg/kg) and high (1.0 mg/kg) doses led to depression-like behaviour in the forced swim and sucrose preference test, while the high dose also induced anxiety-like consequences in the novelty-suppressed feeding test. Electrophysiological recordings revealed both doses to have attenuated serotonergic activity, while the high dose also led to a hyperactivity of noradrenergic neurons only after adolescent exposure. These suggest that long-term exposure to cannabinoids during adolescence induces anxiety-like and depression-like behaviours in adulthood and that this may be instigated by serotonergic hypoactivity and noradrenergic hyperactivity.
慢性青少年期大麻素使用导致的抑郁和焦虑效应的病理生理神经机制可能与单胺能神经递质传递的改变有关。我们通过每天给青少年和成年大鼠腹腔注射一次 CB1 受体激动剂 WIN55,212-2，连续 20 天，然后对它们进行情绪反应测试，并同时进行 5-羟色胺能和去甲肾上腺素能神经元的活体细胞外记录，来验证这一假设。慢性青少年期低剂量（0.2mg/kg）和高剂量（1.0mg/kg）暴露以及成年期低剂量和高剂量暴露均导致强迫游泳和蔗糖偏好测试出现类似抑郁的行为，而高剂量还导致新奇抑制进食测试出现类似焦虑的后果。电生理记录显示两种剂量均减弱了 5-羟色胺能活性，而高剂量仅在青少年期暴露后才导致去甲肾上腺素能神经元的过度活跃。这表明，青少年期长期暴露于大麻素会导致成年期出现类似焦虑和抑郁的行为，而这可能是由 5-羟色胺能活性降低和去甲肾上腺素能活性过度引起的。
