Cadoni C, Pisanu A, Solinas M, Acquas E, Di Chiara G
Department of Toxicology and CNR Center for Neuropharmacology, University of Cagliari, Viale Diaz 182, 09126 Cagliari, Italy.
Psychopharmacology (Berl). 2001 Nov;158(3):259-66. doi: 10.1007/s002130100875.
Repeated exposure to several drugs of abuse has been reported to induce behavioural sensitization. So far no evidence has been provided that such a phenomenon also applies to cannabinoids.
In this study we investigated if repeated exposure to Delta(9)-tetrahydrocannabinol (Delta(9)-THC) induces behavioural sensitization. In addition we tested the possibility of cross-sensitization between Delta(9)-THC and morphine.
Male Sprague-Dawley rats were administered for 3 days, twice daily, with increasing doses of Delta(9)-tetrahydrocannabinol (2, 4 and 8 mg/kg i.p.) or increasing doses of morphine (10, 20 and 40 mg/kg s.c.) or vehicle. After a washout of 14 days the animals were challenged with Delta(9)-THC (75 and 150 microg/kg i.v.), with a synthetic cannabinoid agonist WIN55212-2 (75 and 150 microg/kg i.v.) or with morphine (0.5 mg/kg i.v.), through a catheter inserted into the left femoral vein 24 h before, and the behaviour recorded.
Rats previously administered with Delta(9)-THC showed a greater behavioural activation compared to controls in response to challenge with Delta(9)-THC (150 microg/kg i.v.) and to challenge with morphine (0.5 mg/kg i.v.). Similar to that observed after repeated opiates, this behavioural sensitization was characterized by stereotyped activity. Animals administered with a schedule of morphine that induces behavioural sensitization to morphine also showed a behavioural sensitization to challenge with cannabinoids (Delta(9)-HC and WIN55212-2, 75 and 150 microg/kg i.v.). The effect of the challenge with Delta(9)-THC was prevented by the administration of the CB1 antagonist SR141716A (1 mg/kg i.p.), 40 min beforehand.
The results of the present study demonstrate that repeated exposure to Delta(9)-THC induces behavioural sensitization not only to cannabinoids but also to opiates. This cross-sensitization was symmetrical since rats behaviourally sensitized to morphine were also sensitized to cannabinoids. These observations further support the evidence of an interaction between the opioid and the cannabinoid system and might provide a neurobiological basis for a relationship between cannabis use and opiate abuse.
据报道，反复接触多种滥用药物会诱发行为敏化。到目前为止，尚无证据表明这种现象也适用于大麻素。
在本研究中，我们调查了反复接触Δ⁹-四氢大麻酚（Δ⁹-THC）是否会诱发行为敏化。此外，我们还测试了Δ⁹-THC与吗啡之间交叉敏化的可能性。
雄性Sprague-Dawley大鼠连续3天，每天两次，给予递增剂量的Δ⁹-四氢大麻酚（2、4和8mg/kg腹腔注射）或递增剂量的吗啡（10、20和40mg/kg皮下注射）或溶剂。在洗脱14天后，通过在24小时前插入左股静脉的导管，用Δ⁹-THC（75和150μg/kg静脉注射）、合成大麻素激动剂WIN55212-2（75和150μg/kg静脉注射）或吗啡（0.5mg/kg静脉注射）对动物进行激发，并记录行为。
与对照组相比，先前给予Δ⁹-THC的大鼠在接受Δ⁹-THC（150μg/kg静脉注射）激发和吗啡（0.5mg/kg静脉注射）激发时表现出更大的行为激活。与反复给予阿片类药物后观察到的情况类似，这种行为敏化的特征是刻板行为。按照能诱发对吗啡行为敏化的方案给予吗啡的动物对大麻素（Δ⁹-HC和WIN55212-2，75和150μg/kg静脉注射）激发也表现出行为敏化。预先40分钟给予CB1拮抗剂SR141716A（1mg/kg腹腔注射）可阻止Δ⁹-THC激发的效果。
本研究结果表明，反复接触Δ⁹-THC不仅会诱发对大麻素的行为敏化，还会诱发对阿片类药物的行为敏化。这种交叉敏化是对称的，因为对吗啡产生行为敏化的大鼠对大麻素也敏感。这些观察结果进一步支持了阿片类系统与大麻素系统之间存在相互作用的证据，并可能为大麻使用与阿片类药物滥用之间的关系提供神经生物学基础。
