scholarly journals A Possible Mechanism Underlying the Effectiveness of Acupuncture in the Treatment of Drug Addiction

2008 ◽  
Vol 5 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Chae Ha Yang ◽  
Bong Hyo Lee ◽  
Sung Hoon Sohn
Keyword(s):  
Amino Acids ◽  
Drug Addiction ◽  
Dopamine Release ◽  
Biological Effects ◽  
Basic Mechanism ◽  
Dopamine Neurons ◽  
Brain Neurotransmitter ◽  
Reinforcing Effects ◽  
Abused Drugs ◽  
Behavioral Evidence

Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. While there are still many unanswered questions about the basic mechanisms of acupuncture, some evidence exists to suggest that acupuncture can play an important role in reducing reinforcing effects of abused drugs. The purpose of this article is to critically review these data. The neurochemical and behavioral evidence showed that acupuncture's role in suppressing the reinforcing effects of abused drugs takes place by modulating mesolimbic dopamine neurons. Also, several brain neurotransmitter systems such as serotonin, opioid and amino acids including GABA have been implicated in the modulation of dopamine release by acupuncture. These results provided clear evidence for the biological effects of acupuncture that ultimately may help us to understand how acupuncture can be used to treat abused drugs. Additional research using animal models is of primary importance to understanding the basic mechanism underlying acupuncture's effectiveness in the treatment of drug addiction.

Dopamine D3 receptor agents as potential new medications for drug addiction

2000 ◽  
Vol 15 (2) ◽  
pp. 140-146 ◽  
Author(s):  
B. Le Foll ◽  
J.C. Schwartz ◽  
P. Sokoloff
Keyword(s):  
Drug Addiction ◽  
Dopamine Neurons ◽  
Receptor Subtypes ◽  
Long Term Effects ◽  
Self Administration ◽  
R And D ◽  
Critical Problems ◽  
Dopamine D3 ◽  
Abused Drugs

SummaryAll drugs abused by humans increase dopamine in the shell of nucleus accumbens, which implicate the neurons of this structure in their hedonic and reinforcing properties. Among the various dopamine receptor subtypes, the D1 (D1R) and D3 (D3R) receptors co-localise in accumbal shell neurons. Synergistic D1R/D3R interactions at this level were found on gene expression and during induction and expression of behavioral sensitisation to levodopa in rats bearing unilateral lesions of dopamine neurons. Behavioral sensitisation to abused drugs is a component of their long-term effects. Converging pharmacologic, human postmortem and genetic studies suggest the involvement of the D3R in reinforcing effects of drugs; D3R agonists reduced cocaine self-administration in rats, without disrupting the maintenance of self-administration. These data suggest the use of D3R agonists as partial substitutes to treat cocaine dependence, by affecting its reward component. However, substitution therapies maintain dependence and may be inefficient on drug craving and relapse, which are the unsolved and critical problems in the treatment of drug addiction. Recently, a highly selective and partial D3R agonist was shown to reduce cocaine-associated cue-controlled behaviour in rats, without having any primary intrinsic effects. As drug-associated cues maintain drug-seeking in animals and elicit craving and relapse in humans, such D3R agents have potential therapeutic applications.

Vasopressin and oxytocin analogs with interchanged sequence of amino acids in positions 7 and 8. synthesis and biological effects

1981 ◽  
Vol 46 (9) ◽  
pp. 2136-2139 ◽  
Author(s):  
Ivo Bláha ◽  
Viktor Krchňák ◽  
Milan Zaoral
Keyword(s):  
Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Effects ◽  
Free Flow ◽  
Protecting Groups ◽  
Pressor Effect ◽  
Phase Synthesis ◽  
Antidiuretic Effect

p-Toluenesulfonyl-S-benzylcysteinyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-NG-p-toluenesulfanylarginyl-prolyl-glycineamide (I) and S-benzylcysteinyl-tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-benzylcysteinyl-leucyl-prolyl-glycine amide (III) were prepared by solid phase synthesis. After removal of the protecting groups, closure of the disulfide ring, and purification by continuous free-flow electrophoresis [arginine7, proline8]vasopressin (II) and [leucine7, proline8]oxytocin (IV) were obtained. The antidiuretic effect of II is markedly higher than its pressor effect; IV possesses c. 6% of the uterotonic and c. 10% of the galactogogous effect of oxytocin.

scholarly journals Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 957
Author(s):  
Mamona Nazir ◽  
Muhammad Saleem ◽  
Muhammad Imran Tousif ◽  
Muhammad Aijaz Anwar ◽  
Frank Surup ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Biological Effects ◽  
Structural Diversity ◽  
Chemical Diversity ◽  
Biosynthetic Pathways ◽  
Natural Sources ◽  
Hybrid Compounds ◽  
Anti Inflammatory

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

scholarly journals The tectonigral pathway regulates appetitive locomotion in predatory hunting in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meizhu Huang ◽  
Dapeng Li ◽  
Xinyu Cheng ◽  
Qing Pei ◽  
Zhiyong Xie ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Superior Colliculus ◽  
Dopamine Release ◽  
Dorsal Striatum ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Neuronal Circuitry ◽  
Locomotion Speed ◽  
Brain Circuit ◽  
Goal Directed Behavior

AbstractAppetitive locomotion is essential for animals to approach rewards, such as food and prey. The neuronal circuitry controlling appetitive locomotion is unclear. In a goal-directed behavior—predatory hunting, we show an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to enhance appetitive locomotion in mice. This tectonigral pathway transmits locomotion-speed signals to dopamine neurons and triggers dopamine release in the dorsal striatum. Synaptic inactivation of this pathway impairs appetitive locomotion but not defensive locomotion. Conversely, activation of this pathway increases the speed and frequency of approach during predatory hunting, an effect that depends on the activities of SNc dopamine neurons. Together, these data reveal that the SC regulates locomotion-speed signals to SNc dopamine neurons to enhance appetitive locomotion in mice.

scholarly journals The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration

2021 ◽  
Vol 10 (15) ◽  
pp. 3197
Author(s):  
Yinghao Yu ◽  
Alan Bohan He ◽  
Michelle Liou ◽  
Chenyin Ou ◽  
Anna Kozłowska ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Basolateral Amygdala ◽  
Neural Substrates ◽  
Plasma Corticosterone ◽  
High Plasma ◽  
Paradoxical Effect ◽  
Chronic Morphine ◽  
Morphine Administration ◽  
Abused Drugs ◽  
Effect Hypothesis

A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine’s reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect—reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.

Structural and Functional State of Erythrocyte Membranes at Drug Addiction

2021 ◽  
Vol 18 (1) ◽  
pp. 13-19
Author(s):  
A.I. Rabadanova ◽  
Keyword(s):  
Amino Acids ◽  
Drug Addiction ◽  
Functional State ◽  
Conformational Changes ◽  
Structural Integrity ◽  
Fluorescence Analysis ◽  
Heroin Addiction ◽  
Dimensional Structure ◽  
Erythrocyte Membranes ◽  
Drug Addicts

The steady growth in the number of drug addicts, especially among young people, dictates the need to find ways to prevent and treat this disease. In this regard, there is a need for a more detailed study of the mechanisms of the course of this disease using modern research methods, such as atomic force microscopy and fluorescence analysis of amino acid residues. Purpose of the work: to reveal the structural and functional state of erythrocyte membranes in drug addiction. Materials and methods. The studies were carried out on the erythrocyte membranes of 60 subjects suffering from heroin addiction. The shape and topography of the erythrocyte surface were studied, and spectral analysis of the proteins of the erythrocyte membranes was carried out. Results. The conducted AFM studies of erythrocyte membranes indicate the heterogeneity of the surface mechanical properties of the erythrocyte membranes of drug addicts. The data obtained indicate an acceleration of the aging process of erythrocytes in drug addiction, which goes in two ways: the formation of outgrowths on the plasmolemma, which subsequently die off (echinocytes) and invagination of the plasmolemma of erythrocytes (spherocytes). The fluorescence spectrum of amino acids in erythrocytes of drug addicts is characterized by a significant decrease in the intensity of almost all peaks and a shift of the fluorescence peak to the short-wave region. Findings. With drug addiction, changes in the structural integrity of red blood cells are noted. In people with drug addiction, in comparison with healthy people, there is a higher variability of the morphology of erythrocytes, which is expressed in a significant increase in the proportion of echinocytes and spherocytes against the background of a significant decrease in the number of discocytes. For the membrane proteins of erythrocytes of drug addicts, conformational changes are characteristic, manifested in a decrease in the intensity of fluorescence of aromatic amino acids, which indicates their structural modification and significant vulnerability of the hematopoietic system. They are largely determined by changes in the fluorescence intensity of tryptophan and, to a lesser extent, tyrosine, which indicates the preservation of the three-dimensional structure of the protein.

scholarly journals F-actin-dependent Translocation of the Rap1 GDP/GTP Exchange Factor RasGRP2

2004 ◽  
Vol 279 (19) ◽  
pp. 20435-20446 ◽  
Author(s):  
Mariía J. Caloca ◽  
José L. Zugaza ◽  
Miguel Vicente-Manzanares ◽  
Francisco Sánchez-Madrid ◽  
Xosé R. Bustelo
Keyword(s):  
Signal Transduction ◽  
Amino Acids ◽  
Subcellular Distribution ◽  
Actin Polymerization ◽  
Biological Effects ◽  
Actin Dynamics ◽  
Exchange Factor ◽  
Common Structure ◽  
Direct Association ◽  
P21 Activated Kinase

RasGRPs constitute a new group of diacylglycerol-dependent GDP/GTP exchange factors that activate Ras subfamily GTPases. Despite a common structure, Ras-GRPs diverge in their GTPase specificity, subcellular distribution, and downstream biological effects. The more divergent family member is RasGRP2, a Rap1-specific exchange factor with low affinity toward diacylglycerol. The regulation of RasGRP2 during signal transduction has remained elusive up to now. In this report, we show that the subcellular localization of Ras-GRP2 is highly dependent on actin dynamics. Thus, the induction of F-actin by cytoskeletal regulators such as Vav, Vav2, Dbl, and Rac1 leads to the shift of RasGRP2 from the cytosol to membrane ruffles and its co-localization with F-actin. Treatment of cells with cytoskeletal disrupting drugs abolishes this effect, leading to an abnormal localization of RasGRP2 in cytoplasmic clusters of actin. The use of Rac1 effector mutants indicates that the RasGRP2 translocation is linked exclusively to actin polymerization and is independent of other pathways such as p21-activated kinase JNK, or superoxide production. Biochemical experiments demonstrate that the translocation of RasGRP2 to membrane ruffles is mediated by the direct association of this protein with F-actin, a property contained within its 150 first amino acids. Finally, we show that the RasGRP2/F-actin interaction promotes the regionalized activation of Rap1 in juxtamembrane areas of the cell. These results reveal a novel function of the actin cytoskeleton in mediating the spatial activation of Ras subfamily GTPases through the selective recruitment of GDP/GTP exchange factors.

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