The purpose of this study is to determine 1) whether morphine postconditiong (MPostC) can attenuate the intercellular adhesion molecules-1 (ICAM-1) expression after reoxygenation injury and 2) the subtype(s) of the opioid receptors (ORs) that are involved with MPostC. Human umbilical vein endothelial cells (HUVECs) were subjected to 6 hr anoxia followed by 12 hr reoxygenation. Three morphine concentrations (0.3, 3, 30 microM) were used to evaluate the protective effect of MPostC. We also investigated blockading the OR subtypes' effects on MPostC by using three antagonists (a micro-OR antagonist naloxone, a kappa-OR antagonist nor-binaltorphimine, and a delta-OR antagonist naltrindole) and the inhibitor of protein kinase C (PKC) chelerythrine. As results, the ICAM-1 expression was significantly reduced in the MPostC (3, 30 microM) groups compared to the control group at 1, 6, 9, and 12 hours reoxygenation time. As a consequence, neutrophil adhesion was also decreased after MPostC. These effects were abolished by coadministering chelerythrine, nor-binaltorphimine or naltrindole, but not with naloxone. In conclusion, it is assumed that MPostC could attenuate the expression of ICAM-1 on endothelial cells during reoxygenation via the kappa and delta-OR (opioid receptor)-specific pathway, and this also involves a PKC-dependent pathway.
Animals ; Benzophenanthridines/pharmacology ; Endothelial Cells/cytology/*drug effects/*metabolism ; Endothelium, Vascular/cytology ; Humans ; Intercellular Adhesion Molecule-1/genetics/*metabolism ; Morphine/*pharmacology ; Naloxone/pharmacology ; Naltrexone/analogs & derivatives/pharmacology ; Narcotic Antagonists/pharmacology ; Narcotics/*pharmacology ; Protein Isoforms/metabolism ; Protein Kinase C/antagonists & inhibitors/metabolism ; Receptors, Opioid/metabolism ; Reperfusion Injury/*metabolism ; Signal Transduction/physiology ; Umbilical Veins/cytology

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

AIMTo determine whether testosterone is involved in morphine withdrawal syndrome (WS).

METHODSIn order to induce dependency, rats were treated with subcutaneous injection of morphine (days 1-2, 5 mg/kg; days 3-5, 7.5 mg/kg; days 6-8, 10 mg/kg), and after the last dose of morphine (day 8) WS was induced by intraperitoneal injection of naloxone (1 mg/kg). Wet dog shake (WDS), abdomen writhing (AW), and jumps (J) were recorded as indicators of WS.

RESULTSThe severity of WDS, AW, and J in male rats was greater than that in females. Accordingly, in 4-week castrated and flutamide-treated (10 mg/kg/day for 8 days, i.p.) male rats, WDS, AW, and J were significantly decreased compared to male control rats. Testosterone replacement therapy (10 mg/kg/day for 8 days, i.m.) in 4-week castrated rats restored the severity of WDS, AW, and J behaviors to the level of non-castrated male rats, whereas testosterone potentiated the WDS behavior in non-castrated male rats.

CONCLUSIONIt can be concluded that testosterone might be effectively involved in morphine WS.

Androgen Antagonists ; pharmacology ; Androgens ; pharmacology ; physiology ; Animals ; Behavior, Animal ; Female ; Flutamide ; pharmacology ; Male ; Morphine ; pharmacology ; Morphine Dependence ; physiopathology ; Naloxone ; pharmacology ; Narcotic Antagonists ; pharmacology ; Narcotics ; pharmacology ; Orchiectomy ; Rats ; Rats, Wistar ; Severity of Illness Index ; Substance Withdrawal Syndrome ; physiopathology ; Testosterone ; pharmacology ; physiology

OBJECTIVETo investigate the modulatory effects of morphine on the susceptibility to pentylenetetrazole-induced seizures, and the involvement of endogenous histamine in this process.

METHODSBoth the wild-type (WT) mice and histidine decarboxylase (a key enzyme for histamine biosynthesis) deficient (HDC-KO) mice were subcutaneously injected with different doses of morphine, and 1 hour later the pentylenetetrazole solution (1.5 %) was infused into the tail vein at a constant rate of 0.3 ml/min. The minimal dose of pentylenetetrazole (mg/kg) needed to induce myoclonic jerks and clonus convulsion was recorded as the thresholds of seizures.

RESULTIn WT mice, morphine dose-dependently decreased the thresholds of both myoclonic jerks and clonus convulsion. In HDC-KO mice, morphine at 10 mg/kg only significantly decreased the threshold of myoclonic jerks from (38.6 +/-2.9)mg/kg to (32.5 +/-0.7)mg/kg, but had no significant effect on the threshold of clonus convulsion [from (51.8 +/-2.1)mg/kg to (47.6 +/-1.2)mg/kg]. In addition, the value of decreased myoclonic jerks (15.8 +/-1.4)% and clonus convulsion (8.3 +/-0.9)% thresholds were much lower in HDC-KO mice than in WT mice [(26.1 +/-2.5)% and (20.8 +/-2.4)%, respectively].

CONCLUSIONMorphine can decrease the thresholds of pentylenetetrazole in induction of seizure, and the endogenous histamine may be involved in this process.

Animals ; Disease Susceptibility ; chemically induced ; metabolism ; physiopathology ; Dose-Response Relationship, Drug ; Histamine ; metabolism ; physiology ; Histidine Decarboxylase ; genetics ; metabolism ; Male ; Mice ; Mice, Knockout ; Morphine ; pharmacology ; Myoclonus ; chemically induced ; metabolism ; physiopathology ; Narcotics ; pharmacology ; Pentylenetetrazole ; Random Allocation ; Seizures ; chemically induced ; genetics ; physiopathology ; Sensory Thresholds ; drug effects

OBJECTIVETo examine the effect of acetylcholine (ACh) on the electric activities of pain-excitation neurons (PEN) and pain-inhibitation neurons (PIN) in the hippocampal CA1 area of normal rats or morphinistic rats, and to explore the role of ACh in regulation of pain perception in CA1 area under normal condition and morphine addiction.

METHODSThe trains of electric impulses applied to sciatic nerve were set as noxious stimulation. The discharges of PEN and PIN in the CA1 area were recorded extracellularly by glass microelectrode. We observed the influence of intracerebroventricular (i.c.v.) injection of ACh and atropine on the noxious stimulation-evoked activities of PEN and PIN in the CA1 area.

RESULTSNoxious stimulation enhanced the electric activity of PEN and depressed that of PIN in the CA1 area of both normal and addiction rats. In normal rats, ACh decrease the pain-evoked discharge frequency of PEN, while increased the frequency of PIN. These effects reached the peak value at 4 min after injection of ACh. In morphinistic rats, ACh also inhibited the PEN electric activity and potentialized the PIN electric activity, but the maximum effect appeared at 6 min after administration. The ACh-induced responses were significantly blocked by muscarinic receptor antagonist atropine.

CONCLUSIONCholinergic neurons and muscarinic receptors in the hippocampal CA1 area are involved in the processing of nociceptive information and they may play an analgesia role in pain modulation. Morphine addiction attenuated the sensitivity of pain-related neurons to the noxious information.

Acetylcholine ; administration & dosage ; metabolism ; Adaptation, Physiological ; drug effects ; physiology ; Animals ; Electric Stimulation ; Evoked Potentials ; physiology ; Female ; Hippocampus ; cytology ; metabolism ; Injections, Intraventricular ; Male ; Morphine ; pharmacology ; Morphine Dependence ; metabolism ; Narcotics ; pharmacology ; Neuronal Plasticity ; physiology ; Neurons ; drug effects ; physiology ; Pain ; metabolism ; Pain Threshold ; physiology ; Rats ; Rats, Wistar ; Receptors, Cholinergic ; drug effects ; metabolism ; Sciatic Nerve ; physiopathology ; Signal Transduction ; physiology

INTRODUCTIONThe aim of this study was to determine the prevalence and characteristics of benzodiazepine (BZD) abuse among intravenous opioid users in Singapore.

MATERIALS AND METHODSEligibility criteria for inclusion in this study were all intravenous buprenorphine abusers, who presented to the Community Addictions Management Programme (CAMP) over a 1-year period from February 2005 to January 2006. One hundred and twenty subjects, who consented to the study, completed an interviewer-administered questionnaire and underwent blood test for blood-borne viral infections.

RESULTSThe age of the 120 subjects ranged from 20 to 64 years, with a mean age of 39.0 (SD 8.0) years. The majority of the participants were male (90.0%); 48.3% were Chinese. Ninety-eight (81.7%) patients were using BZDs concomitantly. Midazolam was the most commonly used BZD. Buprenorphine abusers who were concomitantly using BZDs were significantly younger and reported an earlier age of onset of illicit drug abuse as compared to those not using BZDs. Those abusing BZDs were more likely to share syringes (x 2 = 5.8, P = 0.02), and were more likely to be seropositive for hepatitis C virus (x 2 = 4.3, P = 0.04).

CONCLUSIONSThis study highlights the extreme caution that needs to be exercised in prescribing BZDs to all patients in general and patients with injecting drug use or histories of drug abuse in particular. At a public health level, general practitioners (GPs) who prescribe buprenorphine should have compulsory training which highlights the potential dangers of abuse and concomitant abuse of BZDs.

Adult ; Buprenorphine ; pharmacology ; Female ; Humans ; Hypnotics and Sedatives ; pharmacology ; Male ; Midazolam ; pharmacology ; Middle Aged ; Narcotics ; pharmacology ; Prevalence ; Retrospective Studies ; Singapore ; epidemiology ; Substance-Related Disorders ; epidemiology

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

Adult ; Analgesics, Opioid ; pharmacology ; Female ; Fentanyl ; pharmacology ; Humans ; In Vitro Techniques ; Interleukin-6 ; blood ; Male ; Morphine ; pharmacology ; Narcotics ; pharmacology ; Tumor Necrosis Factor-alpha ; analysis

OBJECTIVETo establish the computer-based video-tracking conditioned place preference (CPP) system in mice.

METHODSThe CPP system was composed of computer, camera, soundproof box, shuttle box and analytical software. The results of morphine-induced conditioned place preference were used to evaluate the experiment system. And the effect of morphine-induced locomotor activity in drug-paired compartment was studied in mice.

RESULTSLow (1 mg/kg, i.p.), moderate (3 mg/kg, 5 mg/kg, i.p.) and high (10 mg/kg, i.p.) dose of morphine significantly prolonged the time mice spent in drug-paired compartment compared with saline, but there was no dose-response relation. Moderate and high dose of morphine significantly enhanced locomotor activity, among which 5 mg/kg and 10 mg/kg morphine induced behavior sensitization in drug-paired compartment during the conditioning sessions.

CONCLUSIONThe computer-based video-tracking conditioned place preference experiment system in mice established successfully is reliable and stable.

Animals ; Automatic Data Processing ; Conditioning (Psychology) ; drug effects ; physiology ; Male ; Mice ; Mice, Inbred ICR ; Models, Animal ; Morphine ; pharmacology ; Motor Activity ; drug effects ; Narcotics ; pharmacology ; Opioid-Related Disorders ; physiopathology ; psychology ; Video Recording

No abstract available.
Classification* ; Hallucinogens* ; Narcotics* ; Pharmacology*