Changes Of Preprodynor Phine MRNA And μOpioid Receptor In Morphine Dependent And Abstinent Rats

To observe the inhibitory effect of scopolamine (5pm) and chlorpromazine (Clo) on withdrawal syndromes in morphine dependent rats. We record the intensity of withdrawal syndromes on the model of morphine dependent rats after single or multiple subcutaneous administration(sc) of scopolamine and chlorpromazine in different doses. It was found that withdrawal syndromes were markedly decreased when single scopolamine 1 mg/kg and scopolamine 0.5 mg/kg combined with Mor were injected(P<0.05). Subcutaneous administration(sc) of Spm+Clo have much stronger effects on inhibiting withdrawal syndromes after intraperitoneal (ip) naloxone in morphine dependent rats (P< 0.01). Scopolamine could act on Ach receptor and relieve morphine withdrawal syndromes. Chlorpromazine may have a synergistic action with scopolamine via Q 2-receptor in the locus coeruleus of the rat brainstem. In order to study the effect of ketamine on the withdrawal syndromes of morphine dependent rat. We record the intensity of withdrawal syndromes precipitated by naloxone (5 mg/kg, ip)on the model of morphine dependent rats,after single or multiple times subcutaneous administration (sc) of ketaxnine. We find that withdrawal syndromes were markedly decreased when single ketamine 1 0-20mg/Kg and multiple ketamine 4-8mg/kg were injected(P<0.05). Ketamine is 8 effective in inhibiting withdrawal syndromes of morphine dependent rats which may be related to its inhibition of NOS. To study the changes of u opioid receptor in brain regions of morphine dependent and abstinent rats by light microscopy autoradiography. Thirty SD rats were divided randomly into three groups (n= 10). The rats in dependent group and abstinent group were administered with morphine by intraperitoneal injection till morphine dependent models were founded. The rats in abstinent group were induced withdrawal syndromes with naloxone 5 mg/kg for 24 hours, the rats in control group were injected with saline. All rats were sacrificed by decapitation. The coronal sections of Discrete brain regions (frontal cortex, hippocampus, striatum, thalamus, hypothalamus) were cut. The localization and density of u opioid receptor in all three groups were measured by light microscopy autoradiography. We find that (1) In morphine dependent group, the density of u opioid receptor in frontal cortex, hippocampus, stnatum, thalamus and hypothalamus were significantly lower than those in control group (P<0.0 1). (2) In morphine abstinent group, the density of u opioid receptor in frontal cortex, hippocampus, striatum, thalamus, hypothalamus were significantly higher than those in dependent group (P<0.05 or 0.01). However, the density of u opioid receptor in frontal cortex, hippocampus, striatum, thalamus ,except in hypothalamus (P> 0.05) ,were still significantly 9 lower tban those in control grouP (P<0.01). Morphine dePendence canlower the level of u opioid receptor in rat brain, and after morphinabstinence by naloxone these changes are difficult to recover in shorttenn, which may be involved in the neurobiological mechaisms of opioiddependence and abstinence.TO investigae the effect of longterm adIninistraion of morphine onpreprodynorphin InRNA level in rat hippocamPus.TWenty SD ratswere divided randoInly into tWo grOuPs(n=l0).The rats in morphindependent grouP were adndnistered with morphin b...