Norepinephrine Uptake into Cerebral Cortical Synaptosomes after One Fight or Electroconvulsive Shock

Welch, Bruce L.; Hendley, Edith D.; Turek, Ibrahim

doi:10.1126/science.183.4121.220

Cited by 40 publications

(5 citation statements)

References 7 publications

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“…More recently, chronic subordination stress in tree shrews was found to persistently upregulate alpha 2C receptors in discrete brain stem nuclei, but not in the locus coeruleus or prefrontal cortex (Flügge et al, 1997, 2003). Such findings need to be seen in the context of similar observations in animals that engaged in attack behavior (Welch et al, 1974; Tizabi et al, 1980) and point to a much more general role of noradrenergic activity during social conflict that is not specific to defeat. It will be instructive to learn how activation of norepinephrine and its receptor and transporter molecules are linked with a specific type of social stress, and how this noradrenergic activity is coordinated with those of excitatory amino acids and other amines and peptides.…”

Section: Neurobiological Characteristics Therapeutics and Drug Abusementioning

confidence: 71%

Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake

Miczek

Yap

Covington

2008

Pharmacology & Therapeutics

295

252

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The impact of ostensibly aversive social stresses on triggering, amplifying and prolonging intensely rewarding drug taking is an apparent contradiction in need of resolution. Social stress encompasses various types of significant life events ranging from maternal separation stress, brief episodes of social confrontations in adolescence and adulthood, to continuous subordination stress, each with its own behavioral and physiological profile. The neural circuit comprising the VTA–accumbens–PFC–amygdala is activated by brief episodes of social stress, which is critical for the DA-mediated behavioral sensitization and increased stimulant consumption. A second neural circuit comprising the raphe–PFC–hippocampus is activated by continuous subordination stress and other types of uncontrollable stress. In terms of the development of therapeutics, brief maternal separation stress has proven useful in characterizing compounds acting on subtypes of GABA, glutamate, serotonin and opioid receptors with anxiolytic potential. While large increases in alcohol and cocaine intake during adulthood have been seen after prolonged maternal separation experiences during the first two weeks of rodent life, these effects may be modulated by additional yet to be identified factors. Brief episodes of defeat stress can engender behavioral sensitization that is relevant to escalated and prolonged self-administration of stimulants and possibly opioids, whereas continuous subordination stress leads to anhedonia-like effects. Understanding the intracellular cascade of events for the transition from episodic to continuous social stress in infancy and adulthood may provide insight into the modulation of basic reward processes that are critical for addictive and affective disorders.

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Section: Neurobiological Characteristics Therapeutics and Drug Abusementioning

confidence: 71%

Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake

Miczek

Yap

Covington

2008

Pharmacology & Therapeutics

295

252

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“…Evidence of arousal homeostasis compensating for altered levels of sensory input has also been obtained. At the synaptic level, norepinephrine uptake into cortical synaptosomes is altered by fighting in such a manner as to result in arousal homeostasis (Hendley, Moisset, & Welch, 1973;Welch, Hendley, & Turek, 1974). Electrophysiologically, a number of animal studies (reviewed by Zubeck, 1969) have demonstrated a slowing of cortical EEG rhythms, similar to those observed in sensorily deprived humans, following visual, auditory, or olfactory deafferentation.…”

Section: Evidence For An Arousal Theorymentioning

confidence: 99%

Mechanisms mediating the production of environmentally induced brain changes.

Walsh¹,

Cummins²

1975

Psychological Bulletin

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As yet no satisfactory explanation has been advanced to explain the mechanisms mediating the anatomical and biochemical brain changes induced by exposing animals to environments rich in sensory stimuli. It is hypothesized ' here that a fundamental mechanism is the arousal response, since alterations in arousal appear to be concomitants of all such environmentally induced changes. The properties of the arousal reaction are discussed in terms of their possible relationship to the neurological changes induced, and evidence is presented that this mechanism may be common to several areas of environmental stimulation research which have previously been thought of as separate investigative fields. Several possible tests of the hypothesis are presented, and an underlying cellular response sequence transducing electrical into biosynthetic activity is discussed.Despite the continuing discovery of changes in brain chemistry and anatomy following exposure to environmental stimulation, no satisfactory mechanism has been advanced to explain the mediation of these changes. Postulated physiological mechanisms include stress, endocrine, maturational, and learning factors. Each of these mechanisms and their shortcomings have been discussed by Rosenzweig, Bennett, & Diamond, 1971) and so are dealt with only briefly here. Evidence is then presented to suggest that the arousal reaction (orienting response) may be a major mediating mechanism by showing that the arousal histories of stimulusenriched and stimulus-deprived animals are different and that the properties and consequences of the arousal reaction are such as may account for much current knowledge of enrichment-deprivation effects. First, however, the findings which any hypothesis must hope to explain are briefly reviewed.The brains of animals reared in a complex, as opposed to a stimulus-deprived, environ-The experimental work contributed by the authors was supported by a grant from the Australian Research Grants Committee.We would like to thank Brian Cragg and Marthe Howard for their comments.Requests for reprints should be sent to Robert A.

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“…Even before their cloning, neuroscientists speculated that the regulation of neurotransmitter transporter expression and function could contribute to the plasticity characteristic of neuronal synapses, contributing ultimately to changes in behavior [52, 84, 85]. The availability of molecular tools in the early 1990s provided opportunities to put these speculations to the test [2].…”

Section: Introductionmentioning

confidence: 99%

The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction

Rudnick

Krämer

Blakely

et al. 2013

Pflugers Arch - Eur J Physiol

139

130

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The human SLC6 family is composed of approximately 20 structurally related symporters (co-transporters) that use the transmembrane electrochemical gradient to actively import their substrates into cells. Approximately half of the substrates of these transporters are amino acids, with others transporting biogenic amines and/or closely related compounds, such as nutrients and compatible osmolytes. In this short review, five leaders in the field discuss a number of currently important research themes that involve SLC6 transporters, highlighting the integrative role they play across a wide spectrum of different functions. The first essay, by Gary Rudnick, describes the molecular mechanism of their coupled transport which is being progressively better understood based on new crystal structures, functional studies, and modeling. Next, the question of multiple levels of transporter regulation is discussed by Reinhard Krämer, in the context of osmoregulation and stress response by the related bacterial betaine transporter BetP. The role of selected members of the human SLC6 family that function as nutrient amino acid transporters is then reviewed by François Verrey. He discusses how some of these transporters mediate the active uptake of (essential) amino acids into epithelial cells of the gut and the kidney tubule to support systemic amino acid requirements, whereas others are expressed in specific cells to support their specialized metabolism and/or growth. The most extensively studied members of the human SLC6 family are neurotransmitter reuptake transporters, many of which are important drug targets for the treatment of neuropsychiatric disorders. Randy Blakely discusses the role of posttranscriptional modifications of these proteins in regulating transporter subcellular localization and activity state. Finally, Dennis Murphy reviews how natural gene variants and mouse genetic models display consistent behavioral alterations that relate to altered extracellular neurotransmitter levels.

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Norepinephrine Uptake into Cerebral Cortical Synaptosomes after One Fight or Electroconvulsive Shock

Cited by 40 publications

References 7 publications

Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake

Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake

Mechanisms mediating the production of environmentally induced brain changes.

The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction

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