ABSTRACT
BACKGROUND: Multiple applications of opium medicines can induce the accommodative changes of morphology and function in some intracerebral nerve positions. These accommodative changes are important neurobiological bases inducing drug-desire and re-addiction after detoxification. However, the actual molecular mechanism is unclear at present.OBJECTIVE: To investigate the impacts of the generation of heroin-dependence and detoxification on brain-derived neurotrophic factor (BDNF) in rat to provide a laboratorial gist for the participation of BDNS in heroin-dependence and detoxification.DESIGN: A randomized controlled study by employing experimental animals as subjectsSETTING: Mental health center of a medical university affiliated hospital MATERIALS: The study was conducted in the Laboratory of Pharmacology,Faculty of Pharmacology, Chongqing Medical University between March 2004and July 2004. Totally 30 inbreeding clean male SD rats with a bodymass between 200 g and 250 g were obtained from the Experimental Animal Center of the Third Military Medical University of Chinese PLA. Rats were randomly divided into blank control group(control group), heroin-dependent group (heroin group), and naloxone detoxification group(naloxone group) with 10rats each.METHODS: Morphine was subcutaneously injected into the rat with dose-increasing method to establish heroin-dependence rat model. Rats of naloxone group received subcutaneously injection of 2 mg/kg of naloxone to excite abstinent symptoms. The same dose of normal saline (NS) was injected in rats of control group. Model rats of each group were observed biologically and behaviorally. BDNF expression at different brain zone of rats in three different groups was tested with immunohistochemistry and digoxin-labeled oligonucleoide probe in situ hybridization technique.Comparison of the evaluation of abstinent symptoms in rats of each group.RESULTS: In the heroin group, the relative content of BDNF protein was higher in frontal lobe cortex, locus caeruleus and hippocampus than that of the control group( P ＜ 0.05); BDNFmRNA relative content was higher in frontal lobe cortex than that of the control group( P ＜ 0. 05) . In naloxone group, BDNF and its mRNA relative contents in frontal lobe cortex, locus caeruleus and hippocampus were higher than that of heroin group and control group ( P ＜ 0.05 ).CONCLUSION: Chronic administration of heroin could affect BDNF protein and its mRNA expressions in the corresponding brain areas of the rats, which suggests that the change of BDNF expression participates in heroin-dependence and detoxification.