Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment
Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment
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DOI：
10.1017/s1461145705005651
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发表时间：
2006-06-01
影响因子：
4.8
通讯作者：
Gorzalka, Boris B.
中科院分区：
文献类型：
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作者：
Hill, Matthew N.;Sun, Jane C.;Gorzalka, Boris B.
本研究检测了长期大麻素对5-HT1A和5-HT2A受体的反应性的影响，这两种受体与抑郁症有关。给动物注射强效大麻素受体激动剂HU-210 (100 μ g/kg) 12 d，然后分别对5-HT1A和5-HT2A受体激动剂8-OH-DPAT （0.3 mg/kg）和DOI （1 mg/kg）进行单次刺激，监测动物的行为、生理和激素反应。慢性HU-210治疗可显著增强doi诱导的湿狗抖动，但减少doi诱导的背部肌肉收缩。doi诱导的皮质酮释放不受HU-210治疗的影响。长期HU-210治疗似乎增强了DOI的高温反应，因为50%的受试者死于明显的血清素综合征，核心温度超过43摄氏度。8- oh - dpat诱导的低温反应和皮质酮升高都被长期HU-210治疗显著减弱。这些数据表明，慢性大麻素治疗可能上调5-HT2A受体活性，同时下调5-HT1A受体活性，这一发现与抑郁症中有时观察到的结果相似。这可以部分解释过量吸食大麻与诱发情感性疾病之间的联系。
This study examined the effects of long-term cannabinoid administration on the responsivity of 5-HT1A and 5-HT2A receptors, which have been implicated in depression. Animals received 12 d administration of the potent cannabinoid receptor agonist HU-210 (100 mu g/kg), following which they were monitored on their behavioural, physiological and hormonal responses to a single challenge of a 5-HT1A and 5-HT2A receptor agonist, 8-OH-DPAT (0.3 mg/kg) and DOI (1 mg/kg) respectively. Chronic HU-210 treatment lead to a significant enhancement of DOI-induced wet-dog shakes, but a reduction of DOI-induced back muscle contractions. DOI-induced corticosterone release was unaffected by HU-210 treatment. The hyperthermic response to DOI appeared to be potentiated by long-term HU-210 treatment, as 50% of these subjects died from an apparent serotonin syndrome with core temperatures exceeding 43 degrees C. The 8-OH-DPAT-induced hypothermic response and elevation of corticosterone were both significantly attenuated by long-term HU-210 treatment. These data imply that chronic cannabinoid treatment may up-regulate 5-HT2A receptor activity while concurrently down-regulating 5-HT1A receptor activity, a finding similar to that sometimes observed in depression. This may partially explain the association between excessive cannabis consumption and the induction of affective disease.