OBJECTIVETo analyze the electrical activity property changes in nucleus accumbens (NAc) of heroin-induced conditioned place preference (CPP) rats during different stages of heroin dependence and to explore NAc's roles in the formation of drug dependence.

METHODSRecording electrodes were bilaterally embedded into the NAcs of rats with the aid of stereotaxic apparatus, followed by establishment of heroin-dependent rat model. The NAc electrical activity during 3 different stages of heroin dependence, including heroin pre-exposure, immediate post-exposure and heroin withdrawal, were respectively recorded using EEG wireless telemetry techniques. The frequency distribution (ranging from 0.5 to 30 Hz) and the amplitude of NAc electrical activity were analyzed and measured.

RESULTSHeroin-dependent rat models were successfully established and their withdrawal symptoms were evident. All rats showed a conditioned place preference (CPP) for the white box after 5-10 days of heroin-exposure, and displayed a maximum withdrawal symptoms on 2d after heroin- withdrawal. During all statges of heroin-dependence, the NAc electrical activity contained the highest proportion of delta rhythm and the lowest proportion of alpha2 rhythm. The discharge frequence band was similar across different stages. There was a significantly increased ratio of low-frequency discharges (delta rhythm) and decreased ratio of high-frequency discharges (beta rhythm) in NAc of rats during the immediate post- heroin exposure stage when compared with that during pre-exposure and heroin withdrawal stages. During the withdrawal stage, the ratio of at rhythm was significantly lower than during pre- and post-heroin exposure stages (P < 0.01). Further, the mean discharge amplitude in NAcs during immediate post-exposure and withdrawal stages was significantly increased relative to pre-exposure stage. However, the mean discharge amplitude during heroin withdrawal stage was significantly lower than during immediate post-exposure stage.

CONCLUSIONThe electrical activity properties in rat NAcs showed a significant change during different stages of heroin-dependence, which suggested that neuronal activities in NAcs might contribute to the modulation of drug-dependence.

Animals ; Conditioning, Operant ; Heroin ; pharmacology ; Heroin Dependence ; physiopathology ; Male ; Nucleus Accumbens ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Telemetry

OBJECTIVETo investigate the effects of catecholamine hormone on the blood and brain of heroin addicts.

METHODSRats were divided into three groups and treated with the glucose (control group), the heroin (im) (heroin group), and the combination of the intramuscular injection of reserpine and heroin (reserpine group). Changes in the levels of the dopamine (DA), cAMP, and cGMP were detected by the radioimmunoassay (RIA) method in the blood and brain tissue.

RESULTSNo significant withdrawal symptoms were observed in the reserpine group. Compared with the control and heroin groups, the blood cAMP levels were increased by 35.36% and 15.53% in the reserpine group, respectively; the cAMP levels in the midbrain ventral tegmental area (VTA), prefrontal cortex (PFC), and hippocampus (Hipp) were increased by 24.08% & 8.53%, 15.66% & 8.13%, and 21.95% & 8.40%, respectively. While compared to the control and heroin groups, the DA levels of the PFC, Hipp, striatum, and nucleus accumbens (NAc) were significantly reduced in the reserpine group, decreasing by 74.09% & 82.86%, 81.06% & 82.23%, 91.62% & 86.55% and 84.35% & 90.63%, respectively. The concentrations of cGMP of the brain tissues in the reserpine group were lower than those in the control group. In addition, the neural electrophysiological testing showed that the electroencephalogram (EEG), electrocardiogram (ECG), and muscle spindle discharge diagram of rats in both the reserpine and heroin groups were apparently changed.

CONCLUSIONCatecholamine hormone plays an important role in heroin addiction.

Animals ; Brain ; drug effects ; metabolism ; Catecholamines ; physiology ; Cyclic AMP ; blood ; metabolism ; Cyclic GMP ; blood ; metabolism ; Dopamine ; blood ; metabolism ; Heroin Dependence ; metabolism ; physiopathology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo investigate the changes in orbitofrontal cortex (OFC) functional connectivity and its association with decision-making deficits in chronic heroin-dependent individuals (HDIs) and explore the neural mechanisms of heroin addiction and relapse.

METHODSFourteen male chronic HDIs and 14 healthy subjects matched for age, education, and nicotine consumption participated in this study. Resting state functional magnetic resonance imaging (fMRI) was performed using a 1.5 T MR scanner. Functional connectivity of the OFC and the rest of the brain were calculated using REST software. Voxel-based analysis of the functional connectivity maps between the control and HDI groups was performed with two-sample t test. The Iowa gambling task (IGT) was used to assess the participants' decision making during uncertainty.

RESULTSCompared with the control group, the HDIs showed significantly decreased functional connectivity of the OFC and the right inferior parietal lobule (rIPL) (t=3.5, P<0.05). A significant negative correlation was noted between the functional connectivity of the OFC-rIPL and performance level at the IGT.

CONCLUSIONThe OFC-rIPL functional connectivity is significantly disrupted in HDIs, which may be the neural basis for decision-making deficits.

Adult ; Case-Control Studies ; Decision Making ; Frontal Lobe ; physiopathology ; Heroin Dependence ; physiopathology ; psychology ; Humans ; Magnetic Resonance Imaging ; Male

BACKGROUNDPrevious animal and neuroimaging studies have demonstrated that brain function in heroin addicted users is impaired. However, the posterior cingulate cortex (PCC) has not received much attention. The purpose of this study was to investigate whether chronic heroin use is associated with craving-related changes in the functional connectivity of the PCC of heroin addicted users.

METHODSFourteen male adult chronic heroin users and fifteen age and gender-matched healthy subjects participated in the present study. The participants underwent a resting-state functional magnetic resonance imaging (fMRI) scan and a cue-induced craving task fMRI scan. The activated PCC was identified in the cue-induced craving task by means of a group contrast test. Functional connectivity was analyzed based on resting-state fMRI data in order to determine the correlation between brain regions. The relationship between the connectivity of specific regions and heroin dependence was investigated.

RESULTSThe activation of PCC, bilateral anterior cingulate cortex, caudate, putamen, precuneus, and thalamus was significant in the heroin group compared to the healthy group in the cue-induced craving task. The detectable functional connectivity of the heroin users was stronger between the PCC and bilateral insula, bilateral dorsal striatum, right inferior parietal lobule (IPL) and right supramarginal gyrus (P < 0.001) compared to that of the healthy subjects in the resting-state data analysis. The strength of the functional connectivity, both for the PCC-insula (r = 0.60, P < 0.05) and for PCC-striatum (r = 0.58, P < 0.05), was positively correlated with the duration of heroin use.

CONCLUSIONThe altered functional connectivity patterns in the PCC-insula and PCC-striatum areas may be regarded as biomarkers of brain damage severity in chronic heroin users.

Adult ; Female ; Gyrus Cinguli ; physiopathology ; Heroin Dependence ; pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged

BACKGROUNDStereotactic surgery has been used to treat heroin abstinence in China since 2000 by ablating the amygdaloid nucleus (AMY) and the nucleus accumbens (NAc), which also provides opportunity to identify the relationship between these nuclei and addiction. Our study aimed to explore the physiological and psychological effects of electrically stimulating the AMY and the NAc in heroin addicts after detoxification by observing changes of heart rate, arterial pressure and occurrence of euphoria similar to heroin induced euphoria.

METHODSA total of 70 heroin addicts after detoxification were recruited, and 61 of them were eligible to be given stereotactic surgery for heroin abstinence. The operation was carried out after determining the coordinates of all target nucleuses, and stimulation was performed at the AMY and the NAc solely or jointly. Heart rate, arterial pressure and occurrence of euphoria similar to heroin induced euphoria were recorded and analyzed.

RESULTSThe average heat rate was (66 ± 10) beats/min before electric stimulation, and significantly increased to (84 ± 14) beats/min during stimulation, and changed to (73 ± 12) beats/min 10 minutes after stimulation. There was a significant elevation of the average arterial pressure from 83 mmHg before stimulation to 98 mmHg during the stimulation, and it then decreased to 90 mmHg after stimulation. Forty-three of the 61 patients showed intense euphoria similar to heroin induced euphoria. The largest number (118/186) of euphoric responses occurred when the AMY and the NAc were stimulated at the same time. Odds ratio was 5.4 (95%CI: 2.4 - 11.9, P < 0.0001) to quantify the association. Results from a Logistic regression model showed a positive correlation between unilateral stimulation of either the AMY or NAC and induction of euphoria (OR > 1), especially when the left AMY or left NAc was stimulated (P < 0.05).

CONCLUSIONSOur data are consistent with existing results that the AMY and the NAc are related to addiction. Different roles in drug dependence would be suggested according to the location of the AMY and NAc.

Adolescent ; Adult ; Amygdala ; surgery ; Blood Pressure ; physiology ; China ; Electric Stimulation ; methods ; Female ; Heart Rate ; physiology ; Heroin Dependence ; physiopathology ; psychology ; surgery ; Humans ; Inactivation, Metabolic ; Male ; Nucleus Accumbens ; surgery ; Radiosurgery ; methods ; Young Adult

OBJECTIVETo study the changes of cognitive attention-related brain function in the heroin addicts before and after electro-acupuncture (EA) intervention for exploring the concerned neuro-mechanism of addictive relapse and the central action role of EA intervention.

METHODSAdopting event-related potential (ERP) technique, the ERP at 64 electrode spots in 10 heroin addicts (test group) were recorded before and after EA intervention with dot-probe experimental form during implementing cognitive task on positive emotional clue (PEC), negative emotional clues (NEC), and heroin-related clue (HRC). The P200 amplitude components on the selected observation points (Fz, Cz, and Pz) were analyzed and compared with those obtained from 10 healthy subjects as the control.

RESULTSBefore EA, the ERP of attention on HRC in the test group was higher than that on PEC and NEC (P<0.05) and significantly higher than that in the control group (P<0.05); after EA, the P200 amplitude of attention on HRC at Cz and Pz was significantly lowered (P<0.05) and that on PEC at Fz was significantly elevated (P<0.05). After EA, the P200 amplitude at Pz was ranked as NEC > PEC > HRC, but in the control group, it showed PEC > HRC at all three observation points and PEC > NEC at Pz.

CONCLUSIONHeroin addicts show attention bias to HRC, which could be significantly reduced by EA intervention, illustrating that EA could effectively inhibit the attention bias to heroin and so might have potential for lowering the relapse rate.

Adult ; Attention ; Case-Control Studies ; Cognition ; Electroacupuncture ; Evoked Potentials ; Heroin Dependence ; physiopathology ; therapy ; Humans ; Male ; Substance Withdrawal Syndrome ; physiopathology ; therapy

BACKGROUNDPrevious studies with animal experiments, autopsy, structural magnetic resonance imaging (MRI) and task-related functional MRI (fMRI) have confirmed that brain functional connectivity in addicts has become impaired. The goal of this study was to investigate the alteration of resting-state functional connectivity of the ventral anterior cingulate cortex (vACC) in the heroin abusers' brain.

METHODSFifteen heroin abusers and fifteen matched healthy volunteers were studied using vACC as the region-of interest (ROI) seed. A 3.0 T scanner with a standard head coil was the imagining apparatus. T2*-weighted gradient-echo planar imaging (GRE-EPI) was the scanning protocol. A ROI seed based correlation analysis used a SPM5 software package as the tool for all images processing.

RESULTSThis study showed a functional connection to the insula vACC in heroin abusers. Compared with controls, heroin users showed decreased functional connectivity between the nucleus accumbens (NAc) and vACC, between the parahippocampala gyrus/amgdala (PHC/amygdala) and vACC, between the thalamus and vACC, and between the posterior cingulated cortex/precuneus (PCC/pC) and vACC.

CONCLUSIONThe altered resting-state functional connectivity to the vACC suggests the neural circuitry on which the addictive drug has an affect and reflects the dysfunction of the addictive brain.

Adult ; Female ; Gyrus Cinguli ; pathology ; physiopathology ; Heroin Dependence ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged

OBJECTIVETo evaluate the reliability and validity of the Chinese version of addiction severity index (ASI)-5th version (ASI-C-5), in illegal drug users receiving methadone maintenance treatment (MMT) in China.

METHODSOne hundred and eighty-six heroin addicts (144 men and 42 women) receiving MMT at three clinics in Guizhou province, southwest China, were recruited. They were all interviewed with a questionnaire of ASI-C-5 and 35 were re-interviewed at an interval of seven days to assess its test-retest reliability.

RESULTSCronbach's alpha for internal consistency of CSs varied from 0.60 to 0.81 in all domains. Test-retest reliability of composite scores (CSs) of ASI-C-5 were satisfactory (r=0.38-0.97). Based on item analysis and expert's suggestions, five items were deleted and one item was modified in ASI-C-5. Criterion validity of ASI-C-5 was found acceptable, as compared to addicts' self-rating anxiety scale (SAS) and self-rating depression scale (SDS) (r=0.59 and 0.45) except for social support rating scale (SSRS).

CONCLUSIONSASI-C-5 can be used for heroin addicts receiving MMT with acceptable reliability and validity.

Adult ; China ; Female ; Heroin Dependence ; drug therapy ; physiopathology ; Humans ; Male ; Methadone ; therapeutic use ; Reproducibility of Results ; Severity of Illness Index ; Surveys and Questionnaires

OBJECTIVETo investigate the effect of M(5) muscarinic receptor subtype on the locomotor sensitization induced by heroin priming, and it's effect on the FosB expression in the nucleus accumbens (NAc) and the hippocampus in the heroin sensitized rats.

METHODSLocomotor activity was measured every 10 min for 1 h after subcutaneous injection of heroin. FosB expression was assayed by immunohistochemistry, and the antisense oligonucleotides (AS-ONs) targeting M(5) muscarinic receptor was transferred with the lipofectin.

RESULTSMicroinjection of AS-ONs targeting M(5) muscarinic receptor in the ventral tegmental area (VTA) blocked the expression of behavioral sensitization induced by heroin priming in rats. Meanwhile, the expression of FosB-positive neurons in either the NAc or the dentate gyrus (DG) of the hippocampus increased in heroin-induced locomotor sensitized rats. The enhancement of FosB-positive neurons in the NAc or DG could be inhibited by microinjection of M(5) muscarinic receptor AS-ONs into the VTA before the heroin-induced locomotor sensitization was performed. In contrast, microinjection of M(5) muscarinic receptor sense oligonucleotide (S-ONs) into the VTA did not block the expression of behavioral sensitization or the expression of FosB in the NAc or DG in the heroin sensitized rats.

CONCLUSIONBlocking M(5) muscarinic receptor in the VTA inhibits the expression of heroin-induced locomotor sensitization, which is associated with the regulation of FosB expression in the NAc and hippocampus neurons. M(5) muscarinic receptor may be a useful pharmacological target for the treatment of heroin addiction.

Acetylcholine ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; physiopathology ; Heroin ; adverse effects ; Heroin Dependence ; drug therapy ; metabolism ; physiopathology ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Male ; Microinjections ; Motor Activity ; drug effects ; physiology ; Narcotics ; adverse effects ; Neural Pathways ; drug effects ; metabolism ; physiopathology ; Neurons ; drug effects ; metabolism ; Nucleus Accumbens ; drug effects ; metabolism ; physiopathology ; Oligonucleotides, Antisense ; pharmacology ; Proto-Oncogene Proteins c-fos ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptor, Muscarinic M5 ; antagonists & inhibitors ; genetics ; metabolism ; Synaptic Transmission ; drug effects ; physiology ; Ventral Tegmental Area ; drug effects ; metabolism ; physiopathology

Using wavelet transforms method, time-frequency characteristics of pulse signals from 15 heroin addicts and 15 healthy persons were analyzed. According to 3-D and contour plots used to display discrete dyadic wavelet transforms, the significant difference of time-frequency characteristics between the signals of heroin addicts and healthy persons were revealed. A primary criterion was also obtained,with the criterion, 15 heroin addicts were entirely identified, while two healthy subjects were misidentified. The research result shows that the wavelet-based multiresolution analysis is a very effective method to extract characteristics of pulse signals. It is valuable to the diagnosis and therapy for heroin addicts.
Adult ; Algorithms ; Diagnosis, Computer-Assisted ; Female ; Fourier Analysis ; Heroin Dependence ; diagnosis ; physiopathology ; Humans ; Male ; Medicine, Chinese Traditional ; Pulse ; Signal Processing, Computer-Assisted