Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) Combined with Positron Emission Tomography-Computed Tomography (PET-CT) and Video-Electroencephalography (VEEG) Have Excellent Diagnostic Value in Preoperative Localization of Epileptic Foci in Children with Epilepsy.

BACKGROUND To investigate the effect that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has on surgical decision making relative to video-electroencephalography (VEEG) and positron emission tomography-computed tomography (PET-CT), and if the differences in these variables translates to differences in surgical outcomes. MATERIAL AND METHODS A total of 166 children with epilepsy undergoing preoperative DCE-MRI, VEEG, and PET-CT examinations, surgical resection of epileptic foci, and intraoperative electrocorticography (ECoG) monitoring were enrolled. All children were followed up for 12 months and grouped by Engles prognostic classification for epilepsy. Based on intraoperative ECoG as gold standard, the diagnostic values of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and combined application of DCE-MRI, VEEG, and PET-CT in preoperative localization for epileptic foci were evaluated. RESULTS The sensitivity of DCE-MRI, VEEG, and PET-CT was 59.64%, 76.51%, and 93.98%, respectively; the accuracy of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, and DCE-MRI combined with PET-CT was 57.58%, 67.72%, 91.03%, 91.23%, and 96.49%, respectively. Localization accuracy rate of the combination of DCE-MRI, VEEG, and PET-CT was 98.25% (56/57), which was higher than that of DCE-MRI combined with VEEG and of DCE-MRI combined with PET-CT. No statistical difference was found in the accuracy rate of localization between these three combined techniques. During the 12-month follow-up, children were grouped into Engles grade I (n=106), II (n=31), III (n=21), and IV (n=8) according to postoperative conditions. CONCLUSIONS All DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and DCE-MRI combined with VEEG and PET-CT examinations have excellent accuracy in preoperative localization of epileptic foci and present excellent postoperative efficiency, suggesting that these combined imaging methods are suitable for serving as the reference basis in preoperative localization of epileptic foci in children with epilepsy.

Disrupted white matter structural connectivity in heroin abusers.

Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder.

ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers.

Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.

[Disruption of iron homeostasis and relevant pharmacotherapies in Alzheimer's disease].

Iron is the most abundant metal element to support the body's physiological activities and play crucial roles in the central nervous system. Iron homeostasis is under strict control in normal circumstances, and some diseases will occur once the homeostasis was disrupted. Numerous researches suggest that iron homeostasis disruptes in Alzheimer's disease (AD) and the homeostasis disruption interacts with AD's hallmarks. Dispute still exists on how iron plays a role in AD despite of the great number of researches. This article will focus on iron metabolism, normal function in the brain and recent therapies of AD based on iron chelation.

The comparative risk of developing postoperative complications in patients with distal radius fractures following different treatment modalities.

In this study, we performed a network meta-analysis to compare the outcomes of seven most common surgical procedures to fix DRF, including bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. Published studies were retrieved through PubMed, Embase and Cochrane Library databases. The database search terms used were the following keywords and MeSH terms: DRF, bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. The network meta-analysis was performed to rank the probabilities of postoperative complication risks for the seven surgical modalities in DRF patients. This network meta-analysis included data obtained from a total of 19 RCTs. Our results revealed that compared to DRF patients treated with bridging external fixation, marked differences in pin-track infection (PTI) rate were found in patients treated with plaster fixation, volar plating, and dorsal and volar plating. Cluster analysis showed that plaster fixation is associated with the lowest probability of postoperative complication in DRF patients. Plaster fixation is associated with the lowest risk for postoperative complications in DRF patients, when compared to six other common DRF surgical methods examined.

Pro­angiogenic microRNA­296 upregulates vascular endothelial growth factor and downregulates Notch1 following cerebral ischemic injury.

The present study examined the association between microRNA (miR)­296 and angiogenesis following cerebral ischemic injury, and the underlying mechanisms. A cerebral ischemic model was established in rats via right middle cerebral artery occlusion. The animals were randomly divided into four groups (baseline, 1 day, 3 day and 7 day). Quantitative polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR­296 and hepatocyte growth factor­regulated tyrosine kinase substrate (HGS), respectively. Angiogenesis was assessed by examining microvessel density. The results demonstrated that miR­296 and angiogenesis were significantly upregulated, while HGS was significantly downregulated following ischemic injury. Adenovirus­mediated overexpression of miR­296 markedly enhanced the formation of capillary­like structures in human umbilical vein endothelial cells, parallel with significantly increased expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2, and reduced expression levels of DLL4 and Notch1. The results of the present study provided in vivo and in vitro evidence suggesting that miR­296 promotes angiogenesis in the ischemic brain through upregulating VEGF and downregulating Notch1 following cerebral ischemic injury.

Comparison of Risk of Carpal Tunnel Syndrome in Patients with Distal Radius Fractures After 7 Treatments.

BACKGROUND To compare risk of carpal tunnel syndrome (CTS) in distal radius fracture (DRF) patients after 7 treatments using bridging external fixation (BrEF), non-bridging external fixation (non-BrEF), plaster fixation, K-wire fixation, dorsal plating fixation, volar plating fixation, and dorsal and volar plating by performing a network meta-analysis. MATERIAL AND METHODS An exhaustive search of electronic databases identified randomized controlled trails (RCTs) closely related to our study topic. The published articles were screened, based on predefined inclusion and exclusion criteria, to select high-quality studies for the present network meta-analysis. Data extracted from the selected studies were analyzed using STATA version 12.0 software. RESULTS The literature search and selection process identified 12 eligible RCTs that contained a total of 1370 DRF patients (394 patients with BrEF, 377 patients with non-BrEF, 89 patients with K-wire fixation, 192 patients with plaster fixation, 42 patients with dorsal plating fixation, 152 patients with volar plating fixation, and 124 patients with dorsal and volar plating fixation). Our network meta-analysis results demonstrated no significant differences in CTS risk among the 7 treatments (P>0.05). The value of surface under the cumulative ranking curve (SUCRA), however, suggested that dorsal plating fixation is the optimal treatment, with the lowest risk of CTS in DRF patients (dorsal plating fixation: 89.2%; dorsal and volar plating: 57.8%; plaster fixation: 50.9%; non-BrEF: 50.6%; volar plating fixation: 39.6%; BrEF: 38.4%; K-wire fixation: 23.6%). CONCLUSIONS Our network meta-analysis provides evidence that dorsal plating fixation significantly decreases the risk of CTS and could be the method of choice in DRF patients.

Incubation of alcohol craving during abstinence in patients with alcohol dependence.

Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts.

miR-376b-5p regulates angiogenesis in cerebral ischemia.

The profile of microRNAs (miRNAs) altered following middle cerebral artery occlusion (MCAO) and miRNAs are involved in angiogenesis following cerebral ischemia. miR­376b­5p was decreased following MCAO, however, whether miR­376b­5p is important in angiogenesis remains to be elucidated. The present study was designed to identify whether miR­376b­5p is involved in angiogenesis following cerebral ischemia and to elucidate the underlying mechanisms. A rat MCAO model was established and quantitative polymerase chain reaction was performed to analyze the mRNA expression level of miR­376b­5p for 1 to 7 days. In addition, the density of microvessels and the relative mRNA and protein levels of hypoxia­inducible factor­1 α (HIF­1α), vascular endothelial growth factor A (VEGFA) and Notch1 were measured. The miR­376b­5p mimic or the miR­376b­5p inhibitor were transfected into hypoxic human umbilical vein endothelial cells (HUVECs), and the proliferation, migration and tube formation were measured. To further examine the underlying mechanisms, shRNA was transfected into cells to knock down HIF­1α, and angiogenesis and the expression of associated molecules, including HIF­1α, VEGFA and Notch1 were compared between each group. Our results demonstrated that miR­376b­5p repressed angiogenesis in vivo and in vitro, and miR­376b­5p inhibited angiogenesis in HUVECs by targeting the HIF­1α­mediated VEGFA/Notch1 signaling pathway. These findings provide new insights into angiogenesis therapy for cerebral ischemia.

[Recent progress in vaccines against nicotine addiction].

Tobacco smoking is a global healthcare problem that poses a substantial and costly health burden. Nicotine is the major constituent responsible for the addiction to tobacco. Current strategies helping tobacco smokers have limited utility in increasing rates of smoking cessation, consequently indicating the need for alternative therapies. A novel therapeutic method is vaccination against nicotine. Nicotine vaccine can generate specific antibodies that can sequester nicotine from cigarette smoke in the blood, and prevent its access to the brain and minimize positive reinforcing effects, which may help smokers to stop smoking. The vaccine will have great potential for the treatment of nicotine addiction and for relapse prevention. Here we will review the current status of vaccines against nicotine addiction and discuss the problems associated with the development of nicotine vaccines.

[Effects of air temperature and soil moisture on flavonoids accumulation in Ginkgo biloba leaves].

Taking the 2-year old Ginkgo biloba seedlings as test materials, a pot experiment was conducted in an artificial climate chamber to study the effects of air temperature and soil moisture on the flavonoids accumulation in leaves. Three levels of air temperature (15/5 degrees C, 25/15 degrees C, and 35/25 degrees C day/night) and three levels of soil moisture (55%-60%, 40%-45%, and 30%-35% of field capacity) were installed, yielding nine temperature-soil moisture combinations. Under the three levels of soil moisture, the quercetin, kaempferol, isorhamnetin, and total flavonoids contents in the leaves were higher at 15/5 degrees C than at 25/15 degrees C and 35/25 degrees C. Soil moisture had minor effects on the flavonoids accumulation. The leaf kaempferol content was the highest, followed by quercetin and isorhamnetin. The total flavonoids yield per plant at 35/25 degrees C was higher than that at 15/5 degrees C and 25/15 degrees C. It was suggested that to adopt appropriate soil covering and watering before harvesting to decrease the ambient temperature could benefit the enhancement of leaf flavonoids content and the improvement of per unit area flavonoids production in G. biloba leaf-harvesting plantation.

Clonidine improved laboratory-measured decision-making performance in abstinent heroin addicts.

BACKGROUND: Impulsivity refers to a wide spectrum of actions characterized by quick and nonplanned reactions to external and internal stimuli, without taking into account the possible negative consequences for the individual or others, and decision-making is one of the biologically dissociated impulsive behaviors. Changes in impulsivity may be associated with norepinephrine. Various populations of drug addicts all performed impulsive decision making, which is a key risk factor in drug dependence and relapse. The present study investigated the effects of clonidine, which decreased norepinephrine release through presynaptic alpha-2 receptor activation, on the impaired decision-making performance in abstinent heroin addicts. METHODOLOGY/PRINCIPAL FINDINGS: Decision-making performance was assessed using the original version of Iowa Gambling Task (IGT). Both heroin addicts and normal controls were randomly assigned to three groups receiving clonidine, 0, 75 µg or 150 µg orally under double blind conditions. Psychiatric symptoms, including anxiety, depression and impulsivity, were rated on standardized scales. Heroin addicts reported higher scores on the Barratt Impulsiveness Scale and exhibited impaired decision-making on the IGT. A single high-dose of clonidine improved the decision-making performance in heroin addicts. CONCLUSIONS/SIGNIFICANCE: Our results suggest clonidine may have a potential therapeutic role in heroin addicts by improving the impaired impulsive decision-making. The current findings have important implications for behavioral and pharmacological interventions targeting decision-making in heroin addiction.

1-Benzyl-4-chloro-indoline-2,3-dione.

There are two independent mol-ecules in the asymmetric unit of the title compound, C(15)H(10)ClNO(2), which differ in the dihedral angles between the mean planes of the phenyl ring and the 4-chloro-indoline-2,3-dione ring system [59.48 (9) and 79.0 (1)°]. In the crystal, mol-ecules are linked through C-H⋯O hydrogen bonds, forming polymeric chains in [100].

Drug-related cues exacerbate decision making and increase craving in heroin addicts at different abstinence times.

RATIONALE: Relapse is a persistent problem in the management of addiction. Drug-related cues are powerful instigators of relapse. Impulsive decision making may contribute to relapse through a poorly considered assessment of the consequences of drug use. Drug cues robustly increase subjective craving, which is frequently associated with relapse. OBJECTIVE: The present study explored the effects of drug-related cues on decision making and craving in heroin addicts at different abstinence times: 1, 3, 12, and 24 months. METHODS: The 75 male participants were given 5 min exposure to neutral and drug-associated cues while decision making performance, craving, blood pressure, heart rate, and emotional state pre- and post-exposure were assessed. The Iowa Gambling Task was used to evaluate decision making ability in heroin addicts. RESULTS: Drug-related cues exacerbated impulsive decision making and increased craving, heart rate, and systolic pressure in heroin addicts at all abstinence times. CONCLUSIONS: Drug-related cues aggravated decision making and increased craving in former heroin addicts who had been drug-free for 1-24 months, which might have significant clinical implications for the prevention of relapse.

Effects of stress on decision-making deficits in formerly heroin-dependent patients after different durations of abstinence.

OBJECTIVE: Drug abuse is associated with substantial impairments in decision making. However, little is known about the time course of changes in decision-making ability after abstinence or about the effects of stress on decision making in individuals recovering from heroin dependence after different durations of abstinence. METHOD: First, the authors assessed decision-making performance with the original card version of the Iowa Gambling Task in formerly heroin-dependent patients who had been abstinent for 3, 7, 15, or 30 days or 3, 6, 12, or 24 months. Second, patients who had been abstinent from heroin for 15 or 30 days or 3, 12, or 24 months were challenged with acute stress induced by the Trier Social Stress Test. Third, the ß-adrenoceptor antagonist propranolol (40 mg) was administered 1 hour before stress to those who had been abstinent for 30 days or 12 or 24 months. RESULTS: The short-term abstinence groups (3-30 days) performed worse on the Iowa Gambling Task compared with the long-term abstinence groups (3-24 months). Psychosocial stress unmasked a latent impairment in decision making in the 24-month abstinence group, which seemed to perform identically to healthy comparison subjects in the absence of stress. Propranolol blocked the stress-induced impairment of decision making, which was seen only in the formerly heroin-dependent patients. CONCLUSIONS: Stress can exacerbate an already existing impairment of decision making or unmask a latent one in individuals recovering from heroin dependence. The ß-adrenergic blockade reduces this effect and might hold promise for treatment of substance use disorders.

Multiple 100 Hz electroacupuncture treatments produced cumulative effect on the suppression of morphine withdrawal syndrome: Central preprodynorphin mRNA and p-CREB implicated.

Alleviating opiate withdrawal syndrome in addicts is a critical precondition to break away from drug and further to prevent reuse. Electroacupuncture (EA) was claimed to be effective for alleviating withdrawal syndrome, but the optimal protocol remained unclear. In the present study we found that (1) 100 Hz EA administered 12-24h after the last morphine injection suppressed the withdrawal syndrome in rats, multiple sessions of EA were more effective than single session, with the after-effect lasting for at least 7 days. (2) A down-regulation of preprodynorphin (PPD) mRNA level was observed in spinal cord, PAG and hypothalamus 60 h after the last morphine injection, which could be reversed by multiple sessions, but not a single session of EA. (3) Accompanied with the decrease of PPD mRNA level, there was an up-regulation of p-CREB in the three CNS regions, which was abolished by 100 Hz EA treatment. The findings suggest that down-regulation of p-CREB and acceleration of dynorphin synthesis in spinal cord, PAG and hypothalamus may be implicated in the cumulative effect of multiple 100Hz EA treatment for opioid detoxification.

Construction and characterization of calreticulin-HBsAg fusion gene recombinant adenovirus expression vector.

AIM: To generate recombinant adenoviral vector containing calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine. METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease digestion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5' end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinantion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombinant adenoviral vector to package and amplify recombinant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expression of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting. RESULTS: The CRT-HBsAg fusion gene was characterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HBsAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 x 10(11) pfu/mL. The CRT-HBsAg fusion protein was expressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B virus gene therapy.

[Effects of waterlogging on the growth and energy-metabolic enzyme activities of different tree species].

Aimed to understand the waterlogging tolerance and adaptation mechanisms of different tree species, a simulated field experiment was conducted to study the growth and energy-metabolic enzyme activities of one-year-old seedlings of Taxodium distichum, Carya illinoensis, and Sapium sebiferum. Three treatments were installed, i. e., CK, waterlogging, and flooding, with the treatment duration being 60 days. Under waterlogging and flooding, the relative growth of test tree species was in the order of T. distichum > C. illinoensis > S. sebiferum, indicating that T. distichum had the strongest tolerance against waterlogging and flooding, while S. sebiferum had the weakest one. Also under waterlogging and flooding, the root/crown ratio of the three tree species increased significantly, suggesting that more photosynthates were allocated in roots, and the lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH) activities of the tree species also had a significant increase. Among the test tree species, T. distichum had the lowest increment of LDH and ADH activities under waterlogging and flooding, but the increment could maintain at a higher level in the treatment duration, while for C. illinoensis and S. sebiferum, the increment was larger during the initial and medium period, but declined rapidly during the later period of treatment. The malate dehydrogenase (MDH), phosphohexose (HPI), and glucose-6-phosphate dehydrogenase (G6PDH) -6-phosphogluconate dehydrogenase (6PGDH) activities of the tree species under waterlogging and flooding had a significant decrease, and the decrement was the largest for T. distichum, being 35.6% for MDH, 21.0% for HPI, and 22.7% for G6PDH - 6PGDH under flooding. It was suggested that under waterlogging and flooding, the tree species with strong waterlogging tolerance had a higher ability to maintain energy-metabolic balance, and thus, its growth could be maintained at a certain level.

Repeated 2 Hz peripheral electrical stimulations suppress morphine-induced CPP and improve spatial memory ability in rats.

Our previous studies have shown that 2 Hz peripheral electrical stimulation (PES) can suppress morphine-induced conditioned place preference (CPP) in the rat, although the mechanisms remain unclear. Since CPP involves the mechanism of learning and memory, it is rational to ask whether the suppressive effect of repeated 2 Hz PES on morphine-induced CPP is due to an impairment of the function of spatial learning and memory. Rats were trained with 4 mg/kg morphine, i.p. for 4 days to establish the CPP. Twenty-four hours after the CPP testing, they were given PES at 2 Hz once a day for 1, 3 or 5 days, followed by another CPP testing. The results showed that (1) the morphine-induced CPP was significantly inhibited by 3 or 5 consecutive sessions, but not by single session of 2 Hz PES. (2) A test of spatial leaning and memory ability using the Morris water maze task revealed that 2 Hz PES per se exhibited a promoting, rather than a deteriorating effect on the ability of spatial memory. (3) 2 Hz PES by itself produced a moderate yet significant CPP. The results imply that (a) a low frequency PES can produce a rewarding effect as revealed by the CPP testing, which may account, at least in part, for its suppressive effect on morphine induced CPP, (b) the suppressive effect of PES on morphine induced CPP is not due to a deteriorating effect on the ability of spatial memory.

Repeated peripheral electrical stimulations suppress both morphine-induced CPP and reinstatement of extinguished CPP in rats: accelerated expression of PPE and PPD mRNA in NAc implicated.

Previous studies have shown that peripheral electrical stimulation (PES) can suppress morphine-induced conditioned place preference (CPP) and the reinstatement of extinguished CPP in the rat. The present study was performed to elucidate if preproenkephalin (PPE) and preprodynorphin (PPD) mRNAs in the nucleus accumbens (NAc) play a role in this event. Rats were trained with morphine for 4 days to establish CPP paradigm. They were then given 15-min test once a day for eight consecutive days for extinction trial. Twenty-four hours after the 8th session of extinction trials, rats were given peripheral electrical stimulation (PES) at 2 or 100 Hz once a day for 3 days, then a morphine-priming injection at a dose of 1, 2, or 4 mg/kg to reinstate the extinguished CPP. At the end of the experiment, PPE and PPD mRNA levels in the nucleus acccumbens (NAc) were determined by the semiquantitative RT-PCR technique. The results showed that PES at 2- and 100-Hz administered 30 min a day for 3 days suppressed both the expression of morphine-induced CPP and the reinstatement of extinguished CPP. PES at 2 Hz increased preproenkephalin (PPE) mRNA levels, whereas PES of 100 Hz that of preprodynorphin (PPD) mRNA levels in the NAc. These findings suggest that enkephalin and dynorphin in NAc may play important roles in the mechanisms underlying the inhibitory effect of PES on the expression and reinstatement of morphine-induced CPP in rats.