Schneider Miriam, Schömig Edgar, Leweke F Markus
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Addict Biol. 2008 Sep;13(3-4):345-57. doi: 10.1111/j.1369-1600.2008.00117.x.
Although cannabis belongs to the most widely used drugs among adolescents, little is known about its acute and lasting neurobehavioral effects during critical developmental periods. In the present study we investigated acute and long-term behavioral effects of the cannabinoid agonist WIN 55,212-2 (WIN) in pubertal and adult rats. Chronic WIN (1.2 mg/kg)/vehicle treatment was extended over 25 days throughout puberty, from postnatal day (pd) 40 to pd 65, or for a similar time period in adult rats (> pd 80). All animals were tested at three time points for object/social recognition memory, social interaction and spontaneous social behavior. First, acute cannabinoid effects were investigated directly after the first injection. Additionally, behavioral performance was retested 24 hours and 15 days after cessation of WIN treatment. Chronic pubertal WIN treatment induced persistent object/social recognition deficits, indicating a general impairment in short-term information processing. Lasting disturbances in social behavior, social play and self-grooming were also found. Furthermore, behavioral deficits seen after acute WIN administration were more pronounced in pubertal than in adult rats. These results confirm our recent findings that chronic pubertal cannabinoid treatment leads to lasting behavioral alterations in adulthood, and they show that acute cannabinoid administration induces more severe behavioral deficits in pubertal rats than in mature animals. We therefore conclude that an immature brain is more susceptible to the acute and chronic effects of exogenous cannabinoids than an adult organism, which might be explained by an overactive endocannabinoid system and concomittant maturational disturbances in further neurotransmitter systems during pubertal development.
尽管大麻是青少年中使用最为广泛的毒品之一,但对于其在关键发育阶段的急性和长期神经行为影响却知之甚少。在本研究中,我们调查了大麻素激动剂WIN 55,212-2(WIN)对青春期和成年大鼠的急性和长期行为影响。慢性WIN(1.2毫克/千克)/赋形剂处理在整个青春期从出生后第(pd)40天持续到pd 65天,为期25天,或在成年大鼠(> pd 80)中进行类似时间段的处理。所有动物在三个时间点接受物体/社会识别记忆、社会互动和自发社会行为测试。首先,在首次注射后直接研究急性大麻素效应。此外,在WIN处理停止后24小时和15天对行为表现进行重新测试。青春期慢性WIN处理导致持续的物体/社会识别缺陷,表明短期信息处理普遍受损。还发现社会行为、社会玩耍和自我梳理存在持久障碍。此外,青春期大鼠急性给予WIN后出现的行为缺陷比成年大鼠更明显。这些结果证实了我们最近的发现,即青春期慢性大麻素处理会导致成年期持久的行为改变,并且表明急性给予大麻素在青春期大鼠中比在成熟动物中诱导更严重的行为缺陷。因此,我们得出结论,未成熟的大脑比成年生物体对外源性大麻素的急性和慢性影响更敏感,这可能是由于青春期发育过程中内源性大麻素系统过度活跃以及其他神经递质系统随之出现的成熟障碍所致。