Singh M E, Verty A N A, Price I, McGregor I S, Mallet P E
School of Psychology, University of New England, Armidale, NSW 2351, Australia.
Neuropharmacology. 2004 Dec;47(8):1157-69. doi: 10.1016/j.neuropharm.2004.08.008.
A growing body of evidence suggests the existence of a functional interaction between opioid and cannabinoid systems. The present study further investigated this functional interaction by examining the combined effects of morphine and the cannabinoid receptor antagonist SR 141716 on Fos-immunoreactivity (Fos-IR), a marker for neural activation. Male albino Wistar rats were treated with SR 141716 (3 mg/kg, intraperitoneally), morphine HCl (10 mg/kg, subcutaneously), vehicle, or SR 141716 and morphine combined (n = 6 per group). Rats were injected with morphine or its vehicle 30-min after administration of SR 141716 or its vehicle and perfused 3 h later. Locomotor activity and body temperature were both increased in the morphine-treated group and SR 141716 significantly inhibited these effects. Morphine increased Fos-IR in several brain regions including the caudate-putamen (CPu), cortex (cingulate, insular and piriform), nucleus accumbens (NAS) shell, lateral septum (LS), bed nucleus of the stria terminalis (BNST), median preoptic nucleus (MnPO), medial preoptic nucleus (MPO), hypothalamus (paraventricular, dorsomedial and ventromedial), paraventricular thalamic nucleus (PV), amygdala (central and basolateral nuclei), dorsolateral periaqueductal gray, ventral tegmental area (VTA), and Edinger-Westphal nucleus. SR 141716 alone increased Fos-IR in the cortex (cingulate, insular and piriform), NAS (shell), LS, BNST, hypothalamus (paraventricular, dorsomedial and ventromedial), PV, amygdala (central, basolateral and medial nuclei), VTA, and Edinger-Westphal nucleus. SR 141716 attenuated morphine-induced Fos-IR in several regions including the CPu, cortex, NAS (shell), LS, MnPO, MPO, paraventricular and dorsomedial hypothalamus, PV, basolateral amygdala, VTA, and Edinger-Westphal nucleus (EW). These results provide further support for functional interplay between the cannabinoid and opioid systems. Possible behavioural and physiological implications of the interactive effects of SR 141716 on morphine-induced Fos-IR are discussed.
越来越多的证据表明阿片类和大麻素系统之间存在功能相互作用。本研究通过检测吗啡和大麻素受体拮抗剂SR 141716对Fos免疫反应性(Fos-IR,一种神经激活标志物)的联合作用,进一步研究了这种功能相互作用。将雄性白化Wistar大鼠分为四组,分别腹腔注射SR 141716(3毫克/千克)、皮下注射盐酸吗啡(10毫克/千克)、注射溶剂,或同时注射SR 141716和吗啡(每组n = 6)。在注射SR 141716或其溶剂30分钟后,给大鼠注射吗啡或其溶剂,3小时后进行灌注。吗啡治疗组的运动活动和体温均升高,而SR 141716显著抑制了这些效应。吗啡使包括尾状核-壳核(CPu)、皮质(扣带回、岛叶和梨状皮质)、伏隔核(NAS)壳、外侧隔核(LS)、终纹床核(BNST)、视前正中核(MnPO)、视前内侧核(MPO)、下丘脑(室旁核、背内侧核和腹内侧核)、室旁丘脑核(PV)、杏仁核(中央核和基底外侧核)、背外侧导水管周围灰质、腹侧被盖区(VTA)和动眼神经副核在内的多个脑区的Fos-IR增加。单独使用SR 141716可使皮质(扣带回、岛叶和梨状皮质)、NAS(壳)、LS、BNST、下丘脑(室旁核、背内侧核和腹内侧核)、PV、杏仁核(中央核、基底外侧核和内侧核)、VTA和动眼神经副核的Fos-IR增加。SR 141716减弱了吗啡在包括CPu、皮质、NAS(壳)、LS、MnPO、MPO、室旁核和背内侧下丘脑、PV、基底外侧杏仁核、VTA和动眼神经副核(EW)等多个区域诱导的Fos-IR。这些结果为大麻素和阿片类系统之间的功能相互作用提供了进一步的支持。讨论了SR 141716对吗啡诱导的Fos-IR的相互作用效应可能的行为和生理意义。