Marco E M, Llorente R, Moreno E, Biscaia J M, Guaza C, Viveros M P
Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense, Ciudad Universitaria, C/Jose Antonio Novais 2, 28040 Madrid, Spain.
Behav Brain Res. 2006 Sep 15;172(1):46-53. doi: 10.1016/j.bbr.2006.04.012. Epub 2006 May 26.
We have studied functional interactions between nicotine and the cannabinoid receptor agonist CP 55,940 (CP) in the modulation of behavioural and corticosterone responses of male and female adolescent Wistar rats. The animals underwent a subchronic nicotine treatment (0.4 mg/kg i.p., once daily) during the periadolescent period (postnatal days 34-43). Twenty-four hours after the last injection of nicotine an acute dose of CP (1 or 100 microg/kg i.p.) was administered. Thirty minutes after the cannabinoid injection, the animals were tested individually in the holeboard immediately followed by the elevated plus-maze. We also measured corticosterone levels by radioimmunoassay. In males, neither CP (1 microg/kg) nor nicotine induced any modification in anxiety when administered alone. However, the combination of the two drugs resulted in a significant anxiogenic-like effect. In females, the lower dose of CP was anxiogenic and nicotine, which did not induce any effect per se, prevented this response. In the holeboard, subchronic nicotine and the acute cannabinoid treatment interacted in the modulation of horizontal activity and the nature of this interaction also showed a clear sexual dimorphism. Both, the cannabinoid agonist and nicotine increased corticosterone concentrations and the animals receiving the two drugs showed higher levels than the animals receiving the cannabinoid alone. The data provide evidence for the existence of functional interactions between nicotine and cannabinoids in the modulation of behavioural responses and adrenocortical activity in adolescent rats.
我们研究了尼古丁与大麻素受体激动剂CP 55,940（CP）之间的功能相互作用，该相互作用涉及对雄性和雌性青春期Wistar大鼠行为及皮质酮反应的调节。在青春期（出生后第34 - 43天）期间，对动物进行亚慢性尼古丁处理（腹腔注射0.4 mg/kg，每日一次）。在最后一次注射尼古丁24小时后，给予急性剂量的CP（1或100 μg/kg腹腔注射）。注射大麻素30分钟后，立即在洞板中对动物进行单独测试，随后进行高架十字迷宫测试。我们还通过放射免疫分析法测量了皮质酮水平。在雄性大鼠中，单独给予CP（1 μg/kg）或尼古丁时，均未引起焦虑的任何改变。然而，两种药物联合使用则产生了显著的焦虑样效应。在雌性大鼠中，较低剂量的CP具有致焦虑作用，而尼古丁本身未产生任何效应，但可阻止这种反应。在洞板实验中，亚慢性尼古丁和急性大麻素处理在水平活动调节方面存在相互作用，且这种相互作用的性质也表现出明显的性别差异。大麻素激动剂和尼古丁均增加了皮质酮浓度，同时接受两种药物的动物比仅接受大麻素的动物皮质酮水平更高。这些数据为尼古丁和大麻素在调节青春期大鼠行为反应及肾上腺皮质活动中存在功能相互作用提供了证据。
