Broadband terahertz time-domain spectroscopy of drugs-of-abuse and the use of principal component analysis

EPSRC, the European Community IST FP6 Integrated, etc

Irregular morphine administration affects the retention but not acquisition of conditioned place preference in rats

Drug addiction is increasingly viewed as the expression of abnormal associative learning following repeated exposures to the drugs of abuse Previous I studies have demonstrated that the patterns of repetition such as frequency and spacing are important to many kinds of learning and memory retention We hypothesized that drug repetition pattern might affect the reward-related learning although the total doses of the drug were the same. In the present study, we tested morphine-induced place preference following either regular or irregular pattern of morphine pairing in rats Regular morphine group received morphine administration daily at a regular time with the same dose Irregular morphine groups received morphine administration either at the same time but irregular doses, irregular time but same dose, or irregular time and irregular doses. We found that rats, who received irregular morphine pairing, exhibited similar acquisition of peace preference but different preference retentions compared with regular morphine-treated rats after the same total dose of morphine Rats, who received morphine administration at the same time but irregular doses and at irregular time and irregular doses, showed rapid disruption of place preference than the regular morphine group. Rats, who received morphine at irregular time but the same dose, showed similar retention of place preference to regular morphine group Our results suggest that the pattern of drug pairing plays an important role in the retention of reward-related memory This study may provide new evidence to broaden our understanding of the development and maintenance of drug craving (C) 2009 Elsevier B V. All rights reserved

Dynamic changes in orbitofrontal neuronal activity in rats during opiate administration and withdrawal

The orbitofrontal cortex is involved in the reinforcing effects of drugs of abuse. However, how the dynamic activity in OFC changes during opiate administration and withdrawal period has not been investigated. We first tested the effects of opiates and dr

Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens

Learned association between drugs of abuse and context is essential for the formation of drug conditioned place preference (CPP), which is believed to engage many brain regions including hippocampus, and nucleus accumbens (NAc). The underlying mechanisms

Gender effect on the right-left discrimination task in a sample of heroin-dependent patients

Rationale: Discriminating right from left is an everyday cognitive ability. Repeated exposure to certain drugs, such as heroin, can produce poor performance on many cognitive tasks. However, it is yet unclear whether drug abuse impairs the ability of right-left discrimination. Objectives: The aim of the present study is to examine whether the spatial ability measured by the right-left discrimination task can be affected by heroin abuse and whether such drug effect, if it exists, is gender related. Methods: A paper-and-pen test was used. The test consists of line drawings of a person with no arm, one arm, or both arms crossing the vertical body axis of the figure. The line drawings are viewed from the back, from the front, or randomly alternating between the back and front drawings. The subjects task is to mark which is the right or left hand in the figure as fast as possible. Results: A main finding in this study was that the ability to discriminate between left and right in visual space was impaired in heroin-dependent patients. Especially, heroin-dependent females performed poorer than control females in all conditions but heroin-dependent males only performed poorly in part of conditions. Conclusions: Recent heroin abuse impairs the ability of right-left discrimination and such impairment is gender related: heroin-dependent females demonstrated greater performance deficits than males.

Separation of enantiomers of drugs by capillary electrophoresis with permethyl-gamma-cyclodextrin as chiral solvating agent

High-throughput screening is a promising new approach in analytical chemistry. Within the framework of an extended screening program (The German-Chinese Drug Screening Program), the enantioseparation of 86 drugs was investigated by capillary zone electrophoresis in the presence of the chiral solvating agent (CSA) octakis-(2,3,6-tri-O-methyl)-gamma-cyclodextrin (TM-gamma-CD). By this means, 15 drugs could be separated into enantiomeric pairs. Approximate measures for the degree of interaction (migration retardation factor, R-m) and for the degree of enantiomer recognition (migration separation factors, alpha(m)) revealed intriguing patterns that were compared with those found for native gamma-cyclodextrin (gamma-CD). Although there is a distinct influence of the analyte structure on the electrophoretic data, interpretation remains difficult. Most remarkably, permethylation of gamma-CD leads neither to a higher affinity nor to better chiral recognition, in contrast to the findings with alpha-CD.

Separation and detection of narcotic drugs on a microchip using micellar electrokinetic chromatography and electrochemiluminescence

A new approach for fast and sensitive electrochemiluminescence (ECL) detection of narcotic drugs on a microchip after separation by micellar electrokinetic chromatography (MEKC) is presented, taking the cocaine and its hydrolysate ecgonine as the test analytes. The mixture of hydrophilic BMIMBF4 ionic liquid (IL) and sodium dodecyl sulfate (SDS) was used directly as the buffer of MEKC with less noisy baselines, lower electrophoretic current and satisfactory separation performance.

Physical and spectral characterization of the human cyclin A gene and its interactions with anthracycline anticancer drugs

Over expression of cyclin A in human tumors has been linked to cancer by various experimental lines of evidence. However, physical and spectral characterization of the human cyclin A gene and its interactions with anticancer drugs have not been reported. Our gene sequence analysis, singular value decomposition method and melting studies in the presence of antitumor agents, daunomycin, doxorubicin and Hoechst 33258 showed that cyclin A gene had both AT-rich and GC-rich domains. For a ligand with unknown DNA binding specificity, this gene sequence can be used to differentiate its DNA binding preference.

Field-amplified sample stacking capillary electrophoresis with electrochemiluminescence applied to the determination of illicit drugs on banknotes

Capillary electrophoresis (CE) with Ru(bpy)(3)(2+) electrochemiluminescence. (ECL) detection system was established to the determination of contamination of banknotes with controlled drugs and a high efficiency on-column field-amplified sample stacking (FASS) technique was also optimized to increase the ECL intensity. The method was illustrated using heroin and cocaine, which are two typical and popular illicit drugs. Highest sample stacking was obtained when 0.01 mM acetic acid was chosen for sample dissolution with electrokinetical injection for 6 s at 17 kV. Under the optimized conditions: ECL detection at 1.2 V, separation voltage 10.0 kV, 20 mM phosphate-acetate (pH 7.2) as running buffer, 5 mM Ru(bpy)(3)(2+) with 50 mM phosphate-acetate (pH 7.2) in the detection cell, the standard curves were linear in the range of 7.50 x 10(-8) to 1.00 x 10(-5) M for heroin and 2.50 x 10(-7) to 1.00 x 10(-4) M for cocaine and detection limits of 50 nM for heroin and 60 nM for cocaine were achieved (S/N = 3), respectively. Relative standard derivations of the ECL intensity and the migration time were 3.50 and 0.51% for heroin and 4.44 and 0.12% for cocaine, respectively.The developed method was successfully applied to the determination of heroin and cocaine on illicit drug contaminated banknotes without any damage of the paper currency.

Study of ionizable drugs transfer across the water/1,2-dichloroethane interface with phase volume ratio equal to unity using a three-electrode system

The electrochemical behavior of ionizable drugs (Amitriptyline, Diphenhydramine and Trihexyphenedyl) at the water/1,2-dichloroethane interface with the phase volume ratio (r = V-o/V-w) equal to 1 are investigated by cyclic voltammetry. The system is composed of an aqueous droplet supported at an Ag/AgCl disk electrode and it was covered with an organic solution. In this manner, a conventional three-electrode potentiostat can be used to study the ionizable drugs transfer process at a liquid/liquid interface. Physicochemical parameters such as the formal transfer potential, the Gibbs energy of transfer and the standard partition coefficients of the ionized forms of these drugs can be evaluated from cyclic voltammograms obtained. The obtained results have been summarized in ionic partition diagrams, which are a useful tool for predicting and interpreting the transfer mechanisms of ionizable drugs at the liquid/liquid interfaces and biological membranes.

Studies on electrospray mass spectrometry of some narcotic drugs

Using electrospray ionization (ESI) and tandem mass spectrometry techniques, the protonic positions in protonated molecular ions of some narcotic drugs were studied, The data of ESI/MSn experiments of morphine and deuterium-loaded morphine were first discussed. The protonic position was considered to locate on oxygen atom of cyclic ether in morphine molecular, Compared with the same and different: ions among morphine, codeine, acetylcodeine and dihydrocodeine, the protonic positions in protonated molecular ions of these compounds were further determined. The fragmentation mechanism of morphine in ESI/MSn: experiments was also repored in the paper, and there were similar dehydrolysis mechanism in gas phase or in liquid phase for morphine.