Abstract
Objective To investigate the effect of penehyclidine hydrochloride (PHCD) on tramadol dependence and c-fos,△ FosB and M5 receptor expression in relevant brain regions in rats.Methods Thirty male adult SD rats weighing 180-220 g were randomly assigned to 3 groups (n =10 each):control group (group C),tramadol dependence group (group T) and PHCD group (group P).Tramadol dependence was induced by subcutaneous 10 mg/kg once a day for 7 consecutive days in groups T and P.PHCD 1.5 mg/kg was injected intraperitoneally on day 8 in group P,while in groups C and T the equal volume of normal saline was injected intraperitoneally instead of PHCD.The rats underwent conditioned place perference test at 30 min after intraperitoneal injection.The time spent in drug-paired side (gray area) was recorded.The rats were sacrificed after the conditioned place perference testand the brain was removed.The relevant brain regions (ventral tegmental area,prefrontal cortex,nucleus accumbens )were separated for determination of c-fos,△ FosB expression by Western blot and M5 receptor mRNA expression by RT-PCR.Results Compared with group C,the time spent in the drug-paired side (gray area) was significantly prolonged,and c-fos,△FosB and M5 receptor mRNA expressions were up-regulated in group T,△FosB and Ms receptor mRNA expressions were down-regulated in group P ( P ＜ 0.05 or 0.01 ).There was no significant difference in time spent in the drug-paired side (gray area) and c-fos expression between groups C and P( P ＞ 0.05).Compared with group T,the time spent in the drug-paired side (gray area) was significantly shortened,and c-fos,△ FosB and M5 receptor mRNA expressions were down-regulated in group P (P ＜0.01).Conclusion PHCD can significantly inhibit tramadol dependence by down-regulating c-fos,△FosB and M5 receptor expression in relevant brain regions. Key words: Cholinergic antagonists; Tramadol; Substance-related disorders ; Proto-oncogene proteins c-fos ; Receptors, cholinergic
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