The mechanism of morphine dependent is a complex Procedure. It involves in many complex mechanisms such as the ultra-structure of synapse of special brain areas, neurotransmitter, enzymology, and so on. These mechanisms have closely correlation. In this paper we reveiwed the development in enzymological mechanism of morphine dependent enzymes including protein kinase (PK), nitric oxide synthase (NOS), superoxide dismutase (SOD), adenylate cyclase (AC), Succinate dehydrogenase (SDH)and 3beta-Hydroxy steroid dehydrogenase (3beta-HSD).
Adenylyl Cyclases/metabolism* ; Animals ; Brain/enzymology* ; Morphine Dependence/pathology* ; Nitric Oxide Synthase/metabolism* ; Protein Kinases/metabolism* ; Substance Withdrawal Syndrome/metabolism* ; Succinate Dehydrogenase/metabolism* ; Superoxide Dismutase/metabolism* ; Synapses/enzymology*

AIMTo investigate the effect of CSF contacting neurons (CSF-CNs) lesion in rat dorsal raphe nucleus (DRN) on the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord, and study the relationship between the distal CSF-CNs in rat brain parenchyma and the development of morphine dependence and withdrawal.

METHODSChemical lesion of neurons the injection of cholera toxin subunit B with horseradish peroxidase (CB-HRP) into one of the rats lateral ventricles, TMBST reaction, nNOS immunohistochemistry and Western blot were used in this study.

RESULTSThe withdrawal symptoms by the naloxone precipitated attenuated obviously after the lesion of CSF-CNs in rat DRN, scores of all signs were significantly decreased about 38% compared to that of withdrawal group without lesion (P < 0.05). The withdrawal symptoms scores of vehicle withdrawal group and side lesion withdrawal group were not changed significantly (P > 0.05). Neurons in the location of CSF-CNs concentrated in the rat brain slices of lesion group were damaged obviously, there were only few CB-HRP positive neurons around the lesion location. But the location and the quantity of the CB-HRP positive neurons in the brain slices of the group without lesion was stable relatively, and their appearance was very clear. After the lesion, the nNOS expression and the quantity of the nNOS positive neurons in dorsal horn of spinal cord decreased significantly compared to that of withdrawal group without lesion (P < 0.05), but it also increased significantly compared to that of normal group and dependence group (P < 0.01).

CONCLUSIONThe lesion of distal CSF contacting neurons attenuated the scores of morphine withdrawal symptoms precipitated by naloxone and the nNOS expression in dorsal horn of spinal cord. The distal CSF contacting neurons in rat brain parenchyma partly participated in the development of morphine dependence and naloxone precipitated withdrawal possibly by the modulation of NO (nitric oxide).

Animals ; Brain ; drug effects ; pathology ; Male ; Morphine Dependence ; metabolism ; Neurons ; drug effects ; pathology ; Nitric Oxide Synthase Type I ; metabolism ; Raphe Nuclei ; cytology ; pathology ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome ; metabolism

OBJECTIVETo investigate the effect of NG-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor, on the testis cell apoptosis in morphine-dependent rats induced by naloxone and the involved mechanisms.

METHODSForty-eight Wistar rats were randomly divided into a control group, withdrawal group and a therapeutic group. Morphine-dependent rats were given gradually increasing doses of morphine to produce morphine-dependent models, the abstinent syndrome precipitated by naloxone. The inhibiting effect of L-NNA on the abstinent syndrome, and the testis apoptosis, NOS positive cells, calmodulin (CaM) contents, superoxide dismutase (SOD) activity, and glutathione super oxidase (GSHPx) activity of the morphine-dependent rats induced by naloxone were observed and recorded by radioimmunoassay, atomic absorption spectrometry, in situ nick translation (ISNT) and NADPH-d histochemical technique.

RESULTSCompared with the control rats, the function of the somesthetic motor nerves and autonomic nerves was excessive, the apoptosis and NOS positive cells in the testis were significantly increased (P < 0.05 or P < 0.01), the content of CaM and the activity of SOD and GSHPx were obviously decreased in the morphine-dependent rats induced by naloxone. But L-NNA could significantly inhibit the abstinent syndrome, decrease NOS positive cells and apoptosis, and increase CaM content and the activity of SOD and GSHPx in the testis.

CONCLUSIONMorphine dependence can induce testis cell apoptosis, an increase in testis NOS positive cells, a decrease in CaM content and the activity of SOD and GSHPx in the testis. L-NNA has the curative effect on the morphine abstinent syndrome, protects testis cells against apoptosis and improves their involved biochemical indexes.

Animals ; Apoptosis ; drug effects ; Calmodulin ; biosynthesis ; Disease Models, Animal ; Male ; Morphine Dependence ; pathology ; Nitric Oxide Synthase ; antagonists & inhibitors ; Nitroarginine ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Spermatozoa ; drug effects ; Testis ; pathology

Animals ; Apoptosis ; Male ; Morphine Dependence ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spermatogonia ; metabolism ; pathology ; Spermatozoa ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVE: To observe the changes of adenylate cyclase(AC) on cerebral regions related to morphine dependence in rats and investigate the relationship between the enzymological changes and the mechanism of morphine dependence. METHODS: The technique of enzyme-histochemistry was used to detect the variations of AC of special seven cerebral regions including frontalis cortex, lenticula, corpus amygdaloideun, substantia nigra, hippocampus, periaqueductal gray and locus coerleus in morphine dependent rats. The enzymological changes were observed by optical microscope. Changes of gray degree of these cerebral regions were also observed by using the image analysis system. RESULTS: Compared with those in control group, the contents of AC in morphine dependent groups were increased. CONCLUSION The contents of AC are increase in those regions. The mechanism of morphine dependence close related to the increasing of AC. The correlation of the mechanism of morphine dependence and up-regulation of AC/cAMP-PKA system is discussed.
Adenylyl Cyclases/metabolism* ; Animals ; Brain/pathology* ; Cerebral Cortex/enzymology* ; Disease Models, Animal ; Female ; Hippocampus/enzymology* ; Male ; Morphine Dependence/pathology* ; Periaqueductal Gray/enzymology* ; Rats ; Rats, Sprague-Dawley ; Substance Withdrawal Syndrome/metabolism* ; Time Factors

OBJECTIVETo observe the effects of gamma-aminobutyric acid (GABA) on the electric activities of pain-excited neurons (PEN) in nucleus accumbens (NAc) in central nervous system (CNS) of morphine-dependent rats.

METHODSAfter GABA or the GABA(A)-receptor antagonist, bicuculline (Bic), was injected into cerebral ventricles or NAc, right sciatic nerve was stimulated by electrical pulses, which was considered as traumatic pain stimulation. Extracellular recordings methods were used to record the electric activities of PEN in NAc.

RESULTSWhen GABA was injected into intracerebroventricle (ICV) as well as NAc, it could decrease the pain-evoked discharge frequency and prolong the latency of PEN. Bic could interdict the above effects of GABA on the electric activities of PEN.

CONCLUSIONExogenous GABA might have an inhibitory effect on the central pain adjustment. Furthermore, GABA and GABA(A) receptor participate and mediate the traumatic information transmission process in CNS.

Action Potentials ; drug effects ; physiology ; Animals ; Bicuculline ; pharmacology ; Disease Models, Animal ; Drug Administration Schedule ; Electric Stimulation ; adverse effects ; Female ; GABA Antagonists ; pharmacology ; Injections, Intraventricular ; methods ; Male ; Morphine ; administration & dosage ; Morphine Dependence ; etiology ; pathology ; physiopathology ; Narcotics ; administration & dosage ; Nucleus Accumbens ; metabolism ; physiopathology ; Pain ; etiology ; physiopathology ; Pain Threshold ; drug effects ; physiology ; Rats ; Rats, Wistar ; Reaction Time ; drug effects ; physiology ; Time Factors ; gamma-Aminobutyric Acid ; metabolism ; pharmacology