CHOLECYSTOKININ-B RECEPTOR ANTAGONISM ENHANCES THE ABILITY OF A LOW-DOSE OF MORPHINE TO REDUCE C-FOS EXPRESSION IN THE SPINAL-CORD OF THE RAT

被引:29
作者
CHAPMAN, V [1 ]
HONORE, P [1 ]
BURITOVA, J [1 ]
BESSON, JM [1 ]
机构
[1] ECOLE PRAT HAUTES ETUD,F-75014 PARIS,FRANCE
关键词
D O I
10.1016/0306-4522(95)00085-W
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Three hours after intraplantar carrageenin (6 mg/150 mu l) Fos-like immunoreactivity was predominantly observed in the superficial and deep laminae of the L4-L5 segments of the dorsal horn of the spinal cord in the rat. The total number of Fos-like immunoreactive neurons was equally divided between the superficial (laminae I-II) and deep laminae (laminae V-VI), 99 +/- 3 and 102 +/- 7 Fos-like immunoreactive neurons per section, respectively. In the absence of carrageenin stimulation a negligible number of Fos-like immunoreactive neurons were observed. Pre-administered systemic morphine (0.3 mg/kg) did not significantly influence the total number of Fos-like immunoreactive neurons 3 h after carrageenin. However, pre-administration of a higher dose of morphine (3 mg/kg) significantly reduced the total number of Fos-like immunoreactive neurons (28 +/- 8% reduction, P < 0.001, as compared with control carrageenin Fos-like immunoreactive expression), with this effect being equally divided between the superficial and deep laminae (29 +/- 5 and 29 +/- 6% reduction, respectively, P < 0.001, as compared with control carrageenin Fos-like immunoreactive expression, for both). Pre-administration of the selective cholecystokinin B receptor antagonist, L-365-260 (0.2 mg/kg), alone did not influence the total number of Fos-like immunoreactive neurons 3 h after carrageenin. Co-administration of the ineffective dose of morphine (0.3 mg/kg) and the ineffective dose of L-365-260 (0.2 mg/kg) significantly reduced the total number of Fos-like immunoreactive neurons (23 +/- 5% reduction, P < 0.05, as compared with control carrageenin Fos-like immunoreactive expression), with this effect being equally divided between the superficial and deep laminae (22 +/- 4 and 27 +/- 5% reduction, respectively, P < 0.05, as compared with control carrageenin Fos-like, immunoreactive expression, for both). The effect of co-administered morphine (0.3 mg/kg) and L-365-260 on the total number of Fos-like immunoreactive neurons was significantly different from the lack of effect of the same dose of morphine alone (P < 0.05) and the same dose of L-365-260 alone (P < 0.05), but was not significantly different from the effect of 3 mg/kg of morphine alone. Pre-administration of morphine (3 mg/kg) and L-365-260 (0.2 mg/kg) significantly reduced the total number of Fos-like immunoreactive neurons (34 +/- 5% reduction, P < 0.001, as compared with control carrageenin Fos-like immunoreactive expression), but was not significantly different from the effect of 3 mg/kg of morphine alone. Our results provide evidence that a normally ineffective dose of morphine administered with the cholecystokinin B receptor antagonist, L-365-260, reduces spinal Fos expression associated with prolonged pain processing. However, as illustrated by the lack of interaction between the high dose of morphine and L-365-260, the relationship between the opioids and anti-opioid peptides are not fixed and ubiquitous for all doses of morphine.
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页码:731 / 739
页数:9
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