Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Cocaine-Related Disorders: Disorders related or resulting from use of cocaine.Dopamine Uptake Inhibitors: Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.Crack Cocaine: The purified, alkaloidal, extra-potent form of cocaine. It is smoked (free-based), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term "crack" was derived from the crackling sound made upon igniting of this form of cocaine for smoking.Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Conditioning, Operant: Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.CD40 Ligand: A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.Reinforcement (Psychology): The strengthening of a conditioned response.Fas Ligand Protein: A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.Behavior, Addictive: The observable, measurable, and often pathological activity of an organism that portrays its inability to overcome a habit resulting in an insatiable craving for a substance or for performing certain acts. The addictive behavior includes the emotional and physical overdependence on the object of habit in increasing amount or frequency.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Drug-Seeking Behavior: Activities performed to obtain licit or illicit substances.Behavior, Animal: The observable response an animal makes to any situation.Reinforcement Schedule: A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Extinction, Psychological: The procedure of presenting the conditioned stimulus without REINFORCEMENT to an organism previously conditioned. It refers also to the diminution of a conditioned response resulting from this procedure.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Dopamine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Heroin: A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Benztropine: A centrally active muscarinic antagonist that has been used in the symptomatic treatment of PARKINSON DISEASE. Benztropine also inhibits the uptake of dopamine.Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Reward: An object or a situation that can serve to reinforce a response, to satisfy a motive, or to afford pleasure.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Butyrylcholinesterase: An aspect of cholinesterase (EC 3.1.1.8).Substance Abuse Detection: Detection of drugs that have been abused, overused, or misused, including legal and illegal drugs. Urine screening is the usual method of detection.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Street Drugs: Drugs obtained and often manufactured illegally for the subjective effects they are said to produce. They are often distributed in urban areas, but are also available in suburban and rural areas, and tend to be grossly impure and may cause unexpected toxicity.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.Substance-Related Disorders: Disorders related to substance abuse.Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Heroin Dependence: Strong dependence, both physiological and emotional, upon heroin.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Ventral Tegmental Area: A region in the MESENCEPHALON which is dorsomedial to the SUBSTANTIA NIGRA and ventral to the RED NUCLEUS. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the NUCLEUS ACCUMBENS. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of SCHIZOPHRENIA.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Rats, Long-Evans: An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.Saimiri: A genus of the family CEBIDAE consisting of four species: S. boliviensis, S. orstedii (red-backed squirrel monkey), S. sciureus (common squirrel monkey), and S. ustus. They inhabit tropical rain forests in Central and South America. S. sciureus is used extensively in research studies.Conditioning (Psychology): A general term referring to the learning of some particular response.Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.CD30 Ligand: A membrane-bound tumor necrosis family member found primarily on activated T-LYMPHOCYTES that binds specifically to CD30 ANTIGEN. It may play a role in INFLAMMATION and immune regulation.TNF-Related Apoptosis-Inducing Ligand: A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.Receptors, Dopamine D3: A subtype of dopamine D2 receptors that are highly expressed in the LIMBIC SYSTEM of the brain.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Mice, Inbred C57BLAnalysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Receptors, sigma: A class of cell surface receptors recognized by its pharmacological profile. Sigma receptors were originally considered to be opioid receptors because they bind certain synthetic opioids. However they also interact with a variety of other psychoactive drugs, and their endogenous ligand is not known (although they can react to certain endogenous steroids). Sigma receptors are found in the immune, endocrine, and nervous systems, and in some peripheral tissues.Prenatal Exposure Delayed Effects: The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH.Kinetics: The rate dynamics in chemical or physical systems.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.OX40 Ligand: A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Macaca mulatta: A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.Methadone: A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)Benzazepines: Compounds with BENZENE fused to AZEPINES.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Dextroamphetamine: The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic.Quinpirole: A dopamine D2/D3 receptor agonist.Opioid-Related Disorders: Disorders related or resulting from abuse or mis-use of opioids.Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Tropanes: N-methyl-8-azabicyclo[3.2.1]octanes best known for the ones found in PLANTS.Receptors, Opioid, kappa: A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Discrimination Learning: Learning that is manifested in the ability to respond differentially to various stimuli.Carboxylic Ester Hydrolases: Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Motivation: Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Flupenthixol: A thioxanthene neuroleptic that, unlike CHLORPROMAZINE, is claimed to have CNS-activating properties. It is used in the treatment of psychoses although not in excited or manic patients. (From Martindale, The Extra Pharmacopoeia, 30th ed, p595)4-1BB Ligand: A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms.Choice Behavior: The act of making a selection among two or more alternatives, usually after a period of deliberation.Stereotyped Behavior: Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Putamen: The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.
  • For diagnostic and analytical assays, such information will help in predicting the ligands that have the potential to cross react, depending upon their structural similarity with cocaine. (iastate.edu)
  • Neuropharmacological agents such as antidepressants, anticonvulsants, and antipsychotics have been tested as treatments for cocaine dependence but these medications have yielded negative clinical outcomes ( 12 - 14 ). (frontiersin.org)
  • These transporters interact with multiple psychoactive agents including cocaine, amphetamines and antidepressants. (nih.gov)
  • Antidepressants and cocaine share the ability to alter neuronal signaling by blocking NE and 5HT transport. (acnp.org)
  • Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD: Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. (hmdb.ca)
  • subsequent studies showed that the σ receptors were able to bind a variety of pharmacologically effective drugs, including benzomorphans, neuroleptics, antidepressants, cocaine, peptides related to neuropeptide Y, and neurosteroids (for review, see ref. 3 ), although intriguingly no known natural specific ligand(s) have been discovered. (aacrjournals.org)
  • For the development of non-peptide ligands for the in vivo detection of alterations in density and affinity of such G-protein coupled (GPCRs) peptide receptors the requirements to affinity and pharmacokinetics have been shifted to thresholds markedly distict from classical GPCRs to dissociation constants (scirp.org)
  • discovered that 5-HT 1B R agonists shift the cocaine self-administration (SA) dose-effect function to the left and increase responding on a PR schedule of cocaine reinforcement, suggesting enhanced reinforcing value of cocaine. (frontiersin.org)
  • The efficacy of catalytic antibodies has been demonstrated in rodent models of cocaine overdose and reinforcement, but kinetic constants for all reported antibody catalysts are marginal and, thus, improved rates will be required before clinical development is warranted ( 24 ). (pnas.org)
  • Serotonin1B receptor stimulation enhances cocaine reinforcement. (wikipedia.org)
  • This study supports the idea that 5-HT 1B R agonists may be useful anti-cocaine medications. (frontiersin.org)
  • One of the microcapsule systems includes, in the hairpin-modified acrylamide constructs, and in the subsequent HCR-generated hydrogel shells, the caged sequences of anti-ATP or anti-cocaine aptamers. (rsc.org)
  • Acutely, the cocaine-induced inhibition of monoamine uptake increases synaptic transmission and blocks the inhibitory function of serotonergic autoreceptors by prolonging the residence time of the neurotransmitter in the synaptic space. (drugabuse.gov)
  • While research investigating the neurochemical effects of cocaine has traditionally focused on monoamine systems, recent studies have shown that there are also significant adaptations in glutamate systems [ 2 ], particularly following chronic cocaine exposure [ 3 ]. (pubmedcentralcanada.ca)
  • Coadministration of κ-opioid receptor agonists (κ-agonists) with cocaine prevents alterations in dialysate dopamine (DA) concentration in the nucleus accumbens (Acb) that occur during abstinence from repeated cocaine treatment. (jneurosci.org)
  • The action of κ-agonists on DA uptake or DAT binding, or both, may be the mechanism(s) mediating the previously reported "cocaine-antagonist" effect of κ-opioid receptor agonists. (jneurosci.org)
  • and some have hypothesized that this action of κ-agonists, which functionally opposes the acute effect of cocaine, underlies the cocaine-antagonistic effect of repeated κ-agonists. (jneurosci.org)
  • discovered that mice given the biased β-AR ligands, carvedilol and alprenolol, which function as antagonists of the G protein-mediated pathway and weak agonists of the β-arrestin-mediated pathway, failed to block object recognition memory (ORM) reconsolidation. (sciencemag.org)
  • YZ- 067 decreased the effect of cocaine in a dose-dependentmanner. (elsevier.com)
  • The effect of cocaine on innate and acquired immunity has been extensively investigated. (jrheum.org)
  • A cocaine analogue is a (usually) artificial construct of a novel chemical compound from (often the starting point of natural) cocaine's molecular structure, with the result product sufficiently similar to cocaine to display similarity in, but alteration to, its chemical function. (wikipedia.org)
  • ɑIC50 value for displacement of [3H]cocaine The hydroxylated 2′-OH analogue exhibited a tenfold increase in potency over cocaine. (wikipedia.org)
  • Some jurisdictions such as the USA, Canada, Australia and New Zealand might however consider RTI-121 to be a controlled substance analogue of cocaine on the grounds of its related chemical structure. (bionity.com)
  • Y] CARROLL F I ET AL: "3-Aryl-2-(3'-substituted-1',2',4'-oxadiazol-5'-yl)tropane analogs of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters", J. MED. (epo.org)
  • Cocaine causes a myriad of toxic responses in the neurons: a) it synergizes with viral proteins, Tat and gp120 resulting in exacerbated neuronal apoptosis, b) it causes calcium mobilization and, c) generation of reactive oxygen species. (thescipub.com)
  • On the other hand, combination tests using a fixed dose of CP 93129 (0.3 or 1 microg/side), given into the ventral tegmental area prior to low systemic doses of cocaine (1.25-2.5 mg/kg), increased cocaine discrimination. (unboundmedicine.com)
  • When high doses of cocaine on the descending limb of the cocaine dose-effect function were available, D2 mutant mice self-administered at higher rates than their heterozygous or wild-type littermates, but the ascending limb of the cocaine dose-effect function did not differ between genotypes. (jneurosci.org)
  • Rimcazole dose-dependently decreased Q 0 and EV at both cocaine doses/injection. (springer.com)
  • Under baseline conditions, cocaine maintained dose-dependent increases in cocaine choice and reciprocal decreases in food choice. (aspetjournals.org)
  • Acute effects of the D 3 ligands were less systematic and most consistent with nonselective decreases in cocaine- and food-maintained responding. (aspetjournals.org)
  • D 3 ligands failed to significantly modify total cocaine intake but caused persistent decreases in food intake. (aspetjournals.org)
  • These results demonstrate that κ-opioid receptor activation modulates DA uptake in the Acb in a manner opposite to that of cocaine: repeated U-69593 administration decreases the basal rate of DA uptake, and acute U-69593 administration transiently increases DA uptake. (jneurosci.org)
  • Furthermore, repeated exposure to cocaine can alter the mechanisms underlying transmitter release in response to a depolarizing agent and decreases the efficiency of sodium and calcium channels in the plasma membrane. (drugabuse.gov)
  • These include both intracellular sodium channel blocker anesthetics and stimulant dopamine reuptake inhibitor ligands (such as certain, namely tropane-bridged-excised, piperidines). (wikipedia.org)
  • Cocaine is a strong stimulant that is most frequently used as a recreational drug. (hmdb.ca)
  • The stimulant and hunger suppression properties of cocaine and coca leaf extracts have been known for thousands of years by indigenous groups in central and South America. (hmdb.ca)
  • Surprisingly, cocaine-induced locomotion was sensitized regardless of whether the mice had received repeated saline or cocaine. (frontiersin.org)
  • A control experiment in noninjected, drug-naïve mice showed that CP94253 had no effect on spontaneous or cocaine-induced locomotion. (frontiersin.org)
  • Mice with a global knockout of β-arrestin2 exhibited impaired memory reconsolidation in ORM, Morris water maze, and cocaine-conditioned place preference experiments. (sciencemag.org)
  • METHODS: We investigated the ability of cocaine and food to induce a CPP in mice lacking either the GluR1 or GluR2 subunits of the AMPA receptor [gria1 or gria2 knockout (KO) mice]. (biomedsearch.com)
  • Recent research coupling the neurobiology of reward with the neurochemical sequelae of repeated cocaine administration indicates that adaptations within the dopamine system occur but do not alone underlie the enduring aspects of drug abuse. (drugabuse.gov)
  • This is a list of cocaine analogues. (wikipedia.org)
  • Within the scope of analogous compounds created from the structure of cocaine, so named "cocaine analogues" retain 3β-benzoyloxy or similar functionality (the term specifically used usually distinguishes from phenyltropanes, but in the broad sense generally, as a category, includes them) on a tropane skeleton, as compared to other stimulants of the kind. (wikipedia.org)
  • The creation of the following analogues of cocaine have traditionally required a step which has utilized 2-CMT as an intermediate molecular product. (wikipedia.org)
  • analogues were synthesized as sigma ligands. (umsystem.edu)