| Opioids dependence has been the critical social and medical problem all over the world.The research on the mechanism and therapeutic countermeasure of opioids dependence is notonly the social emergency, but also the important research content of neurobiology. There havebeen much progress on the studies of mechanism opioids dependence in behavior,neuro-biochemical, celluar and molecular levels. At present, the adaptive up-regulation of thecAMP pathway is widely supposed to participate in the occurrence and the development ofopioids dependence. The cellular adaptations of opioids denpendence, includes both thefunctional adaptation of cell and the morphological adaptation.The adaptations in function andmorphology lead to the compensatory changes in physiology, biochemistry process and tissuestructure, and finally reach the pathological banlance.Autonamic nervous system,especallysympathetic nervous system is relevant closely to opioids dependence. The studies between thesympathetic nervous system and opioids dependence have been carried out in the many brainnuclei associated with sympathetic nervous system.Some studes indicated that peripheralsympathetic nervous system possibly participated in the formation of opioids dependence, butdirect evidence was deficient.We have investigated the effects of morphine on synaptictransmission, cellular signal transduction and morphology, especially ultrastracture, insympathetic ganglia of rats by using multiple methods of intracellular recording technique,radioimmunoassay,immumohistochemistry, RT-PCR and electron microscope.Part I Effects of morphine on synaptic transduction in sympathetic ganglia of ratsThe isolated sympathetic ganglia, superior cervical ganglia (SCG), were established fromcontrol and morphine dependent rats respectively. The acute and chronic effects and mechanismsof morphine on synaptic transmission in SCG were studied by using intracellular recordingtechnique.1. The results came from isolated SCG of normal rats showed that(1) At concentration from 10-4mol/L to 10-3mol/L, morphine reversibly depressed, completely orpartly, f-EPSPs or orthodromic AP, induced by preganglionic nerve stimulation, in the greatmajority SCG neurons(39/42).(2) Morphine (10-3mol/L) had no influence on RMP, Rm and direct AP, induced by cellularup-threshold stimulation, of the great majority SCG neurons (9/10), but induced membranedepolarization in individual SCG neuron (1/10).The membrane depolarization, with averageamplitude of 10.83±1.61mV and average duration of 11.67±1.26min( 3 times in the sameneuron) , did not associate with the significant change of Rm.(3) Morphine (10-3mol/L) reversibly depressed the amplitude of the spike after hyperpolarizationpotential (AHP) .(4) Morphine (10-3mol/L) inhibited the membrane depolarization induced by exogenous ACh andCarb in most SCG neurons (7/10), caused no influence in a few SCG neurons (3/10).(5) Naloxone (10-4mol/L) had no significantly effect on f-EPSP, direct AP and RMP, Rm, butdepressed the inhibitory effect on f-EPSP of morphine(5×10-4mol/L).(6) High Ca2+ (10mmol/L) weakened the inhibitory effect on f-EPSPs of morphine (1×10-3mol/L)2. The results came from the isolated SCG of morphine dependent ratsThe isolated SCG were continually superfused with 5 umol/L morphine in order to maintainthe dependence of the samples.(1) No significant difference of RMP, Rm and direct AP was founded between the SCG neuronsof normal and morphine dependent rats.(2) The inhibitory effects on f-EPSPs of morphine (5×10-4mol/L and 1×10-3mol/L) in SCGneurons of morphine dependent rats, were obviously decreased, compared with the inhibitoryeffects of morphine at the same concentration in normal rats. All the cells didn't associate withthe significant changes of RMP and Rm.(3) Naloxone (1×10-4mol/L) reversibly increased the amplitude of f-EPSPs in SCG neurons ofmorphine dependent rats,the average increased percentage was 49.22±21.66%. A few SCGneurons discharged orthodromic AP. All the cells didn't associate with the significant changes...
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