dynorphins and Heroin-Dependence

Prodynorphin (PDYN) binds to k-opioid receptors (KOPr; encoded by OPRK1) and is known to regulate dopaminergic tone, making this system important for drugs addiction. Dynorphin (Dyn)/KORr system are powerful effectors of stress-induced alterations in reward processing and dysphoric states. Thus, We identified 11 potential functional SNPs and one variable number of tandem repeat (VNTR) in this system, performed a case-control association analysis, investigated particular disease phenotypes, assessed the joint effect of variants in two genes, carried out a meta-analysis to analyze the association between this VNTR and Heroin dependence (HD) risk. Eleven single-nucleotide polymorphisms (SNPs) were genotyped using SNaPshot SNP technology. Participants included 566 healthy controls and 541 patients with HD. We found that PDYN polymorphisms modulate the susceptibility to HD. An increased risk of HD was significantly associated with H alleles of PDYN VNTR (χ

Topics: Analgesics, Opioid; Asian People; Dynorphins; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Genotype; Heroin Dependence; Humans; Polymorphism, Single Nucleotide; Receptors, Opioid, kappa

To explore the clinical effect and mechanism of electroacupuncture at Jiaji (EX-B 2) on drug craving of heroin addicts.. One hundred and twenty cases of heroin addicts were randomly divided into 4 groups, 30 cases in each. In acupuncture group 1, the Jiaji (EX-B 2) points of T5-T7 and Shenshu (BL 23) were selected with electroacupuncture; in acupuncture group 2, Neiguan (PC 6), Shenmen (HT 7) and Zusanli (ST 36) etc. were selected with electroacupuncture; in simulation group, Zusanli (ST 36) and Sanyinjiao (SP 6) were selected with analog electrical stimulation, and in blank group no any therapy was applied. The changes of drug craving were evaluated by Visual Analogue Scale (VAS) and the changes of beta-EP and Dyn-A in plasma before and after treatment were tested by radioimmunoassay.. The relapse rate of 77.3% (17/22) in acupuncture group 1 was lower than those of 88.5% (23/26) in acupuncture group 2, 90.5% (19/21) in simulation group and 95.7% (22/23) in blank group (all P < 0.05). At the 8th and 10th week of treatment, the VAS scores in acupuncture group 1 and 2 were much lower than those in blank group and simulation group (all P < 0.01); in which, it was lower in acupuncture group 1 than that in acupuncture group 2 (P < 0.05), and lower in simulation group than that in blank group. After 10 weeks of treatment, compared with the status before treatment, beta-EP and Dyn-A in plasma were increased in acupuncture group 1 and 2 (P < 0.05, P < 0.01), Dyn-A was decreased in both simulation and blank groups (both P < 0. 01) which was less obvious than those in both acupuncture groups (both P < 0.01) and superior in acupuncture group 1 than that in group 2 (P < 0.05).. Electroacupuncture at Jiaji (EX-B 2) can suppress the drug craving and reduce the relapse rate, and the mechanism may be related with the content of beta-EP, especially the increase of Dyn-A in plasma.

Topics: Acupuncture Points; Adolescent; Adult; beta-Endorphin; Dynorphins; Electroacupuncture; Female; Heroin Dependence; Humans; Male; Middle Aged; Treatment Outcome; Young Adult

This study assessed the clinical effectiveness, physiological responses and also adverse effects of dynorphin in heroin dependent detoxication. The subjects were randomly assigned into three groups and received intravenous injections of dynorphin at the dose of 180 (6 patients) or 60 (7 patients) or 0 (8 patients) micrograms/kg three times a day for 6 days. There was no statistical difference in withdrawal syndrome between each group. However, the drug craving feeling in the dynorphin groups was reduced when compared to the placebo group. There was no report of any adverse effects of the drug or abnormal laboratory results from the subjects during the study period.

Topics: Adult; Dynorphins; Heroin Dependence; Humans; Male; Prognosis; Substance Withdrawal Syndrome

The effectiveness of dynorphin-(1-13) in suppressing heroin withdrawal was studied. At a dose of 60 micrograms/kg body weight, dynorphin-(1-13) was effective in suppressing withdrawal symptoms. When saline was administered a strong placebo effect was noticed that, however, did not influence the outcome of the results. Only three out of the twelve patients receiving dynorphin-(1-13) experienced some mild side-effects such as feeling warm, dizziness and precordial formication.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Dynorphins; Endorphins; Heroin Dependence; Humans; Male; Substance Withdrawal Syndrome

Prenatal cannabis exposure is a growing concern with little known about the long-term consequences on behavior and neural systems relevant for reward and emotional processing.. We used an animal model to study the effects of prenatal exposure to Delta(9)-tetrahydrocannabinol (THC) on heroin self-administration behavior and opioid neural systems in adult males (postnatal day 62). Rats were exposed to THC (.15 mg/kg) or vehicle from gestational day 5 to postnatal day 2.. Both pretreatment groups showed similar heroin intake, but THC-exposed rats exhibited shorter latency to the first active lever press, responded more for low heroin doses, and had higher heroin-seeking during mild stress and drug extinction. THC exposure reduced preproenkephalin (PENK) mRNA expression in the nucleus accumbens during early development, but was elevated in adulthood; no adult striatal changes on preprodynorphin mRNA or PENK in caudate-putamen. PENK mRNA was also increased in the central and medial amygdala in adult THC-exposed animals. THC animals had reduced heroin-induced locomotor activity and nucleus accumbens mu opioid receptor coupling.. This study demonstrates enduring effects of prenatal THC exposure into adulthood that is evident on heroin-seeking behavior during extinction and allostatic changes in mesocorticolimbic PENK systems relevant to drug motivation/reward and stress response.

Topics: Analysis of Variance; Animals; Autoradiography; Behavior, Animal; Cannabis; Conditioning, Operant; Dynorphins; Enkephalins; Female; Guanosine 5'-O-(3-Thiotriphosphate); Heroin Dependence; In Situ Hybridization; Limbic System; Pregnancy; Prenatal Exposure Delayed Effects; Protein Binding; Protein Precursors; Rats; Rats, Long-Evans; Reaction Time