NEURO (A)<428>
Database EMBASE
Accession Number 2005168663
Authors Gong J.-P. Liu Q.-R. Zhang P.-W. Wang Y. Uhl G.R.
Institution
(Gong, Liu, Zhang, Uhl) Molecular Neurobiology, NIDA-IRP, NIH, 333 Cassell Drive, Baltimore, MD21224, United States.
(Wang) Molecular Neuropsychiatry, NIDA-IRP, NIH, 5500 Nathan Shock Drive, Baltimore, MD21224, United States.
Country of Publication
United Kingdom
Title
Mouse brain localization of the protein kinase C-enhanced phosphatase 1 inhibitor KEPI (Kinase C-Enhanced PP1 Inhibitor).
Source
Neuroscience. 132(3)(pp 713-727), 2005. Date of Publication: 2005.
Abstract
We recently identified the protein kinase C-enhanced protein phosphatase 1 (PP1) inhibitor KEPI based on its morphine-induced upregulation in striatum. Regulation of protein serine/threonine dephosphorylation by PP1 can modulate important brain signaling pathways. To improve understanding of KEPI's role in the brain, we have developed anti-KEPI sera in rabbits immunized with a hemocyanin conjugate of KEPI residues 66-80, characterized the specificity that this serum provides, mapped the distribution of immunoreactive KEPI (iKEPI) in mouse brain, rat dorsal root ganglia and striatal cultures and documented KEPI binding to PP1 in vitro. Staining is found in apparently neuronal processes and, often less intensely, in neuronal perikarya in primary cultures and in neurons and neuronal elements from a number of brain regions. iKEPI fiber/terminal patterns are relatively densely distributed in striatum, nucleus accumbens, septum, bed nucleus of the stria terminalis, hippocampus, paraventricular thalamus, ventromedial hypothalamus, interpeduncular nucleus, raphe nuclei, nucleus caudalis of the spinal tract of the trigeminal and dorsal horn of the spinal cord. iKEPI-positive cell bodies lie in the nucleus accumbens, striatum, lateral septal nucleus, granular layer of dentate gyrus, interpeduncular nucleus, dorsal root ganglia and cerebellar vermis. These expression patterns point to possible roles for KEPI in regulating protein dephosphorylation by inhibiting PP1 activities in a number of brain pathways likely to use several different neurotransmitters and to participate in a number of brain functions. Dense KEPI immunoreactivity in nucleus accumbens perikarya, combined with evidence for its regulation by opiates, supports possible roles for KEPI in molecular signal transduction pathways important for drug reward and addiction. copyright 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
ISSN 0306-4522
Publication Type Journal: Article
Journal Name Neuroscience
Volume 132
Issue Part 3
Page 713-727
Year of Publication 2005
Date of Publication 2005
NEURO (GENETICS)<430>
Database EMBASE
Accession Number 2005165489
Authors Hiroi N. Agatsuma S.
Institution
(Hiroi, Agatsuma) Dept. of Psychiat. and Behav. Sci., AlbertEinsteinCollege of Medicine, Bronx, NY, United States.
(Hiroi) Department of Neuroscience, AlbertEinsteinCollege of Medicine, Bronx, NY, United States.
(Hiroi) Lab. of Molecular Psychobiology, Dept. of Psychiat. and Behav. Sci., AlbertEinsteinCollege of Medicine, Bronx, NY10461, United States.
Country of Publication
United Kingdom
Title
Genetic susceptibility to substance dependence.
Source
Molecular Psychiatry. 10(4)(pp 336-344), 2005. Date of Publication: Apr 2005.
Abstract
Despite what is often believed, the majority of those who experiment with substances with a dependence potential do not develop dependence. However, there is a subpopulation of users that easily becomes dependent on substances, and these individuals exhibit pre-existing comorbid traits, including novelty seeking and antisocial behavior. There appears to be a genetic basis for the susceptibility to dependence and these comorbid traits. Animal studies have identified specific genes that can alter susceptibility to dependence and response to novelty. The mechanisms underlying the genetic susceptibility to dependence and response to novelty are complex, but genetic susceptibility plays a significant role in the transition from substance use to dependence and from chronic use to addiction. We discuss two models to explain how genetic variations alter dependence susceptibility. Identification of the specific genes involved in these processes would help to identify individuals that are vulnerable to dependence/addiction and to devise novel treatment strategies. copyright 2005 Nature Publishing Group All rights reserved.
ISSN 1359-4184
Publication Type Journal: Review
Journal Name Molecular Psychiatry
Volume 10
Issue Part 4
Page 336-344
Year of Publication 2005
Date of Publication Apr 2005
NEURO<433>
Database EMBASE
Accession Number 2005158828
Authors Cauli O. Morelli M.
Institution
(Cauli, Morelli) Department of Toxicology, Ctr. Excellence Neurbio. Dependence, University of Cagliari, Cagliari, Italy.
(Cauli) Laboratory of Neurobiology, Fund. Valenciana de Invest. Biomed., Valencia, Spain.
(Morelli) Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
Country of Publication
United Kingdom
Title
Caffeine and the dopaminergic system.
Source
Behavioural Pharmacology. 16(2)(pp 63-77), 2005. Date of Publication: Mar 2005.
Abstract
Caffeine is the most widely consumed psychostimulant substance, being self-administered throughout a wide range of conditions and present in numerous dietary products. Due to its widespread use and low abuse potential, caffeine is considered an atypical drug of abuse. The main mechanism of action of caffeine occurs via the blockade of adenosine A<sub>1</sub> and A<sub>2A</sub> receptors. Adenosine is a modulator of CNS neurotransmission and its modulation of dopamine transmission through A<sub>2A</sub> receptors has been implicated in the effects of caffeine. This review provides an updated summary of the results reported in the literature concerning the behavioural pharmacology of caffeine and the neurochemical mechanisms underlying the psychostimulant effects elicited by caffeine. The review focuses on the effects of caffeine mediated by adenosine A<sub>2A</sub> receptors and on the influence that pre-exposure to caffeine may exert on the effects of classical drugs of abuse. copyright 2005 Lippincott Williams & Wilkins.
ISSN 0955-8810
Publication Type Journal: Review
Journal Name Behavioural Pharmacology
Volume 16
Issue Part 2
Page 63-77
Year of Publication 2005
Date of Publication Mar 2005
NEURO<466>
Database EMBASE
Accession Number 2005118200
Authors Arnsten A.F.T. Ramos B.P. Birnbaum S.G. Taylor J.R.
Institution
(Arnsten, Ramos, Birnbaum) Department of Neurobiology, Yale University, School of Medicine, New Haven, CT 06510, United States.
(Taylor) Department of Psychiatry, Yale University, School of Medicine, New Haven, CT 06510, United States.
(Birnbaum) BaylorCollege of Medicine, Houston, TX77030, United States.
Country of Publication
United Kingdom
Title
Protein kinase A as a therapeutic target for memory disorders: Rationale and challenges.
Source
Trends in Molecular Medicine. 11(3)(pp 121-128), 2005. Date of Publication: Mar 2005.
Abstract
cAMP-dependent protein kinase A (PKA) signaling has a key role in memory processes and has been identified as a potential therapeutic target for memory disorders. The activation of PKA signaling is crucial for the consolidation of long-term memories dependent on the hippocampus and/or the amygdala, By contrast, initial studies indicate that cAMP-PKA activation might impair the working memory and executive functions of the prefrontal cortex. Furthermore, PKA activation in the nucleus accumbens might increase sensitivity to addiction. These complexities must be heeded when designing medications aimed at altering PKA activity. PKA might be most practical as a therapeutic target in disorders with global alterations in cAMP-PKA activity due to genetic or environmental factors. copyright 2005 Elsevier Ltd. All rights reserved.
ISSN 1471-4914
Publication Type Journal: Review
Journal Name Trends in Molecular Medicine
Volume 11
Issue Part 3
Page 121-128
Year of Publication 2005
Date of Publication Mar 2005
NEURO <470>
Database EMBASE
Accession Number 2005107713
Authors Redinbo M.R. Potter P.M.
Institution
(Redinbo) Department of Chemistry, Dept. of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-3290, United States.
(Potter) Department of Molecular Pharmacology, St. Jude Children's Res. Hospital, Memphis, TN 38105-2794, United States.
Country of Publication
United Kingdom
Title
Mammalian carboxylesterases: From drug targets to protein therapeutics.
Source
Drug Discovery Today. 10(5)(pp 313-325), 2005. Date of Publication: 01 Mar 2005.
Abstract
Our understanding of the detailed recognition and processing of clinically useful therapeutic agents has grown rapidly in recent years, and we are now able to begin to apply this knowledge to the rational treatment of disease. Mammalian carboxylesterases (CEs) are enzymes with broad substrate specificities that have key roles in the metabolism of a wide variety of clinical drugs, illicit narcotics and chemical nerve agents. Here, the functions, mechanism of action and structures of human CEs are reviewed, with the goal of understanding how these proteins are able to act in such a non-specific fashion, yet catalyze a remarkably specific chemical reaction. Current approaches to harness these enzymes as protein-based therapeutics for drug and chemical toxin clearance are described, as well as their uses for targeted chemotherapeutic prodrug activation. Also included is an outline of how selective CE inhibitors could be used as co-drugs to improve the efficacy of clinically approved agents. copyright2005 Elsevier Ltd. All rights reserved.
ISSN 1359-6446
Publication Type Journal: Review
Journal Name Drug Discovery Today
Volume 10
Issue Part 5
Page 313-325
Year of Publication 2005
Date of Publication 01 Mar 2005
NEURO<473>
Database EMBASE
Accession Number 2005103001
Authors Chinta S.J. Andersen J.K.
Institution
(Chinta, Andersen) Buck Institute for Age Research, Neurobiology Department, 8001, Redwood Blvd, Novato, CA94945, United States.
Country of Publication
United Kingdom
Title
Dopaminergic neurons.
Source
International Journal of Biochemistry and Cell Biology. 37(5 SPEC. ISS.)(pp 942-946), 2005. Date of Publication: May 2005.
Abstract
Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the mammalian central nervous system. Their loss is associated with one of the most prominent human neurological disorders, Parkinson's disease (PD). Dopaminergic neurons are found in a 'harsh' region of the brain, the substantia nigra pars compacta, which is DA-rich and contains both redox available neuromelanin and a high iron content. Although their numbers are few, these dopaminergic neurons play an important role in the control of multiple brain functions including voluntary movement and a broad array of behavioral processes such as mood, reward, addiction, and stress. Studies into the developmental pathways which are involved in the generation of dopaminergic neurons in the brain have led to the identification of several specific transcription factors including Nurr1, Lmx1b and Pitx3, all shown to be important in the development of the mesencephalic dopaminergic system. The selective degeneration of these dopaminergic neurons in the substantia nigra pars compacta leads to PD but the exact cause for this nigral cell loss is still unknown. copyright 2004 Elsevier Ltd. All rights reserved.
ISSN 1357-2725
Publication Type Journal: Review
Journal Name International Journal of Biochemistry and Cell Biology
Volume 37
Issue Part 5 SPEC. ISS.
Page 942-946
Year of Publication 2005
Date of Publication May 2005
NEURO <485>
Database EMBASE
Accession Number 2005055186
Authors Samaha A.-N. Robinson T.E.
Institution
(Samaha, Robinson) Department of Psychology, University of Michigan, Ann Arbor, MI48109-1109, United States.
Country of Publication
United Kingdom
Title
Why does the rapid delivery of drugs to the brain promote addiction?
Source
Trends in Pharmacological Sciences. 26(2)(pp 82-87), 2005. Date of Publication: Feb 2005.
Abstract
It is widely accepted that the more rapidly drugs of abuse reach the brain the greater their potential for addiction. This might be one reason why cocaine and nicotine are more addictive when they are smoked than when they are administered by other routes. Traditionally, rapidly administered drugs are thought to be more addictive because they are more euphorigenic and/or more reinforcing. However, evidence for this is not compelling. We propose an alternative (although not mutually exclusive) explanation based on the idea that the transition to addiction involves drug-induced plasticity in mesocorticolimbic systems, changes that are manifested behaviourally as psychomotor and incentive sensitization. Recent evidence suggests that rapidly administered cocaine or nicotine preferentially engage mesocorticolimbic circuits, and more readily induce psychomotor sensitization. We conclude that rapidly delivered drugs might promote addiction by promoting forms of neurobehavioural plasticity that contribute to the compulsive pursuit of drugs.
ISSN 0165-6147
Publication Type Journal: Review
Journal Name Trends in Pharmacological Sciences
Volume 26
Issue Part 2
Page 82-87
Year of Publication 2005
Date of Publication Feb 2005
NEURO (GENETICS)<494>
Database EMBASE
Accession Number 2005048577
Authors Yuferov V. Nielsen D.A. Butelman E.R. Kreek M.J.
Institution
(Yuferov, Nielsen, Butelman, Kreek) Lab. of the Biol. of Addictive Dis., Rockefeller University, New York, NY, United States.
(Yuferov) Lab. of the Biol. of Addictive Dis., RockefellerUniversity, 1230 York Avenue, New York, NY10021, United States.
Country of Publication
United Kingdom
Title
Microarray studies of psychostimulant-induced changes in gene expression.
Source
Addiction Biology. 10(1)(pp 101-118), 2005. Date of Publication: Mar 2005.
Abstract
Alterations in the expression of multiple genes in many brain regions are likely to contribute to psychostimulant-induced behaviours. Microarray technology provides a powerful tool for the simultaneous interrogation of gene expression levels of a large number of genes. Several recent experimental studies, reviewed here, demonstrate the power, limitations and progress of microarray technology in the field of psychostimulant addiction. These studies vary in the paradigms of cocaine or amphetamine administration, drug doses, route and also mode of administration, duration of treatment, animal species, brain regions studied and time of tissue collection after final drug administration. The studies also utilize different microarray platforms and statistical techniques for analysis of differentially expressed genes. These variables influence substantially the results of these studies. It is clear that current microarray techniques cannot detect small changes reliably in gene expression of genes with low expression levels, including functionally significant changes in components of major neurotransmission systems such as glutamate, dopamine, opioid and GABA receptors, especially those that may occur after chronic drug administration or drug withdrawal. However, the microarray studies reviewed here showed cocaine- or amphetamine-induced alterations in the expression of numerous genes involved in the modulation of neuronal growth, cytoskeletal structures, synaptogenesis, signal transduction, apoptosis and cell metabolism. Application of laser capture microdissection and single-cell cDNA amplification may greatly enhance microarray studies of gene expression profiling. The combination of rapidly evolving microarray technology with established methods of neuroscience, molecular biology and genetics, as well as appropriate behavioural models of drug reinforcement, may provide a productive approach for delineating the neurobiological underpinnings of drug responses that lead to addiction.
ISSN 1355-6215
Publication TypeJournal: Article
Journal Name Addiction Biology
Volume 10
Issue Part 1
Page 101-118
Year of Publication 2005
Date of Publication Mar 2005
NEURO <499>
Database EMBASE
Accession Number 2005038703
Authors Elliott J.M. Beveridge T.J.R.
Institution
(Elliott) LeicesterSchool of Pharmacy, De MontfortUniversity, LeicesterLE1 9BH, United Kingdom.
(Beveridge) Dept. of Physiology/Pharmacology, Wake Forest Univ. School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1083, United States.
Country of Publication
United Kingdom
Title
Psychostimulants and monoamine transporters: Upsetting the balance.
Source
Current Opinion in Pharmacology. 5(1)(pp 94-100), 2005. Date of Publication: Feb 2005.
Abstract
Monoamine transporters were originally associated simply with the termination of synaptic monoamine function. In addition to amine reuptake, however, the transporters can act as ion channels that affect exocytotic neurotransmitter release and can operate in reverse mode, mediating non-exocytotic amine release. Activity at the plasma membrane is controlled by trafficking, which is modulated by interaction with both substrates and inhibitors and by cytosolic kinases and phosphatases. Monoamine transporters also constitute the principal sites of action of many psychoactive drugs, including amphetamines and cocaine, as well as therapeutic drugs for the treatment of depression, addiction and attention deficit hyperactivity disorder, each modifying the balance of presynaptic neurotransmitter function. copyright 2005 Elsevier Ltd. All rights reserved.
ISSN 1471-4892
Publication Type Journal: Review
Journal Name Current Opinion in Pharmacology
Volume 5
Issue Part 1
Page 94-100
Year of Publication 2005
Date of Publication Feb 2005
NEURO (GENETICS)<502>
Database EMBASE
Accession Number 2005038693
Authors Rhodes J.S. Crabbe J.C.
Institution
(Rhodes, Crabbe) VA MedicalCenter, 3710 SW US Veterans Hospital Road, Portland, OR97239, United States.
Country of Publication
United Kingdom
Title
Gene expression induced by drugs of abuse.
Source
Current Opinion in Pharmacology. 5(1)(pp 26-33), 2005. Date of Publication: Feb 2005.
Abstract
The transition from infrequent drug use to addiction (i.e. the loss of control over consumption of a drug) probably involves changes in gene expression that restructure neural circuits in the brain. The number of genes that have been demonstrated to change expression in response to drugs has increased rapidly in recent years owing to microarray technology, which allows measurement of thousands of genes at one time. It is now important to identify which of these changes are causally related to the compulsive behavior associated with drug addiction, and which are non-specific changes related to general features of arousal or other physiological responses (e.g. stress, altered body temperature or energy metabolism). copyright 2005 Elsevier Ltd. All rights reserved.
ISSN 1471-4892
Publication Type Journal: Review
Journal Name Current Opinion in Pharmacology
Volume 5
Issue Part 1
Page 26-33
Year of Publication 2005
Date of Publication Feb 2005
NEURO <503>
Database EMBASE
Accession Number 2005038692
Authors Jones S. Bonci A.
Institution
(Jones) Department of Anatomy, University of Cambridge, Downing Street, CambridgeCB2 3DY, United Kingdom.
(Bonci) Ernest Gallo Clinic/Research Center, Department of Neurology, Univ. of California, San Francisco, 5858 Horton Street, Emeryville, CA 94608, United States.
Country of Publication
United Kingdom
Title
Synaptic plasticity and drug addiction.
Source
Current Opinion in Pharmacology. 5(1)(pp 20-25), 2005. Date of Publication: Feb 2005.
Abstract
Recent studies have suggested that the development of addictive behaviours shares common features with traditional learning models. Synaptic plasticity, a possible substrate for learning, has been demonstrated in neural reward circuits and might contribute to the learning of addictive behaviours. Changes in the strength of synaptic connections have been investigated in dopaminergic cells of the ventral tegmental area in response to several addictive drugs. Rapid and persistent forms of synaptic plasticity (specifically, long-lasting synaptic potentiation) have been demonstrated to accompany some of the behavioural effects of addictive drugs. We hypothesize that drug-induced synaptic plasticity might play a role in reward-related learning and addiction by modifying the fine tuning of dopaminergic cell firing. copyright 2005 Elsevier Ltd. All rights reserved.