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  • 1
    Electronic Resource
    Electronic Resource
    Serotonin Enhances Striatal Dopamine Outflow In Vivo Through Dopamine Uptake Sites (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Serotonin (5-HT) administered at 1, 3, and 10 µM into the striatum of halothane-anesthetized rats by in vivo microdialysis increased extracellular dopamine (DA) in a concentration-dependent manner (approximately 65, 190, and 440%, respectively). These effects were reduced by 50% in the presence of 1 µM tetrodotoxin (TTX) or in the absence of Ca2+ ions. The DA uptake blocker nomifensine (0.1 µM) significantly lowered (by 50%) the enhancement of DA outflow induced by 3 µM 5-HT. Nomifensine (1 µM) coperfused with 1 µM TTX abolished the 1 and 3 µM 5-HT-induced DA outflow, whereas the effect of 10 µM 5-HT was significantly reduced by 1 (−55%) and 10 µM (−70%) nomifensine. These data demonstrate that, in vivo, striatal DA uptake sites are partially involved in the DA-releasing action of 5-HT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.66010210.x
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  • 2
    Electronic Resource
    Electronic Resource
    d-Fenfluramine Increases Striatal Extracellular Dopamine In Vivo Independently of Serotonergic Terminals or Dopamine Uptake Sites (1995)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 65 (1995), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of various doses of the serotonin (5-HT) release-inducing agent d-fenfluramine (d-fenf) on extracellular dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) was studied in vivo in the striatum of halothane-anesthetized rats, following systemic and local administration. At 5 and 10 but not 2.5 mg/kg, d-fenf administered intraperitoneally significantly increased DA extracellular concentration and reduced DOPAC outflow. A concentration-dependent enhancement of DA dialysate content was also found following intrastriatal application (5, 10, 25, and 50 µM). The bilateral administration of 5,7-dihydroxytryptamine into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum, did not modify the effect on extracellular DA concentration of 25 µM d-fenf locally applied into the striatum. The enhancement of extracellular DA level induced by 25 µM d-fenf was slightly but significantly reduced by the local application of 25 µM citalopgram. The blockade of DA uptake sites by nomifensine (0.1, 0.3, and 1 µM) did not modify significantly the effect of d-fenf. The rise of DA outflow induced by 25 µM d-fenf was strongly reduced in the presence of 1 µM tetrodotoxin (TTX) or by the removal of Ca2+ from the perfusion medium. The results obtained show that d-fenf increases the striatal extracellular DA concentration by a Ca2+-dependent and TTX-sensitive mechanism that is independent of striatal 5-HT itself or DA uptake sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1995.65031100.x
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  • 3
    Electronic Resource
    Electronic Resource
    Functional heterogeneity in dopamine release and in the expression of Fos-like proteins within the rat striatal complex (1999)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The dorsolateral striatum, and the core and shell of the nucleus accumbens are three major anatomical regions of the striatal complex. The shell is considered as a part of the extended amygdala, and is involved in the control of motivation and reward. The core and the striatum are considered central to sensory motor integration. In this study we compared the responses of these three regions to mild stress and drugs of abuse by measuring extracellular dopamine (DA) concentrations and Fos-like immunoreactivity (Fos-LI). The results are summarrized as follows. (i) In unchallenged conditions, extracellular DA concentrations were highest in the dorsolateral striatum and lowest in the core, whereas Fos-LI was highest in the shell and lowest in the dorsolateral striatum. (ii) After challenges that increase DA by depolarizing DAergic neurons (injection stress or 2 mg/kg morphine), the shell presented the largest increase in DA levels and Fos-LI. (iii) After the administration of a DA-uptake blocker (15 mg/kg cocaine), the percentage increase in DA was still largest in the shell. However, the absolute increase in DA and Fos-LI in the shell and the dorsolateral striatum were similar. (iv) After a full D1 agonist (SKF82958), Fos-LI was highest in the shell and lowest in the dorsolateral striatum. In conclusion, the nucleus accumbens shell seems to be the area of the striatal complex most functionally reactive to stress and drugs of abuse. However, the dorsolateral striatum and the core appear functionally distinct, as for most of the parameters studied these two regions differed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1999.00525.x
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  • 4
    Electronic Resource
    Electronic Resource
    Cocaine self-administration increases the incentive motivational properties of the drug in rats (1999)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A progressive increase in the frequency and intensity of drug use is one of the major behavioural phenomena characterizing the development of addiction. The nature of the drug-induced adaptations involved in this escalating drug intake remains unknown. Some theories propose that this escalation is due to a progressive decrease (tolerance) in the reinforcing or incentive effects of the drug. Alternative views posit that with chronic use the reinforcing or incentive effects of drugs increase, by a sensitization or a learning mechanism. In this report, we address the question of whether escalating cocaine intake is paralleled by an increase or a decrease in the reinforcing and incentive effects of the drug. Using the experimental model of intravenous drug self-administration with a within-session dose–response paradigm, we first studied the course of cocaine intake over 14 sessions in rats. After acquisition of cocaine self-administration, cocaine intake progressively increased at each dose tested. Then rats, previously allowed to self-administer cocaine during either six or 29 sessions, were compared in three different tests of the incentive and reinforcing effects of cocaine: cocaine-induced reinstatement of self-administration, cocaine-induced runway and cocaine-induced place conditioning. As compared with rats briefly exposed to cocaine self-administration (six sessions), rats with the longer experience (29 sessions) exhibited a higher intake of cocaine paralleled by a higher responsiveness in the cocaine-induced reinstatement and runway tests. Both groups of rats were similarly sensitive to the rewarding effects of the drug as evaluated by the threshold dose of cocaine inducing place conditioning. Our results demonstrate that escalating cocaine intake is paralleled by an increase in the motivational properties of the drug in the absence of apparent signs of tolerance to the reinforcing or incentive effects of cocaine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1999.00696.x
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  • 5
    Electronic Resource
    Electronic Resource
    Individual differences in stress-induced dopamine release in the nucleus accumbens are influenced by corticosterone (1998)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Stressful experiences, glucocorticoids hormones and dopaminergic neurons seems to interact in determining a higher propensity to develop drug abuse. In this report, we studied the acute interaction between these three factors. For this purpose, we compared stress-induced dopamine release in intact rats and in rats in which stress-induced corticosterone secretion was experimentally blocked. Ten-minute tail-pinch was used as a stressor and dopamine release estimated in the nucleus accumbens by using the microdialysis technique. Individual differences were also taken into account by comparing rats identified as either predisposed (HRs) or resistant (LRs) to develop self-administration of drugs of abuse, on the basis of their locomotor response to novelty. It was found that suppression of stress-induced corticosterone secretion significantly decreased stress-induced dopamine release. However, such an effect greatly differed between HR and LR rats. When corticosterone secretion was intact HR animals had a higher and longer dopamine release in response to stress than LRs. The blockade of stress-induced corticosterone secretion selectively reduced the dopaminergic response of HRs that did not differ from LRs anymore. These findings strength the idea that glucocorticoids could be involved in determining propensity to develop drug self-administration. In particular, these hormones could play a role in determining the higher dopaminergic activity that characterizes drug proned individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1998.00438.x
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  • 6
    Electronic Resource
    Electronic Resource
    Neurochemical characterization of individual vulnerability to addictive drugs in rats (1998)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 10 (1998), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Rats exposed to a low-light, low-noise, novel environment exhibit differences in individual locomotor response to the novelty stressor. The categorization of rats in a locomotor screening procedure as low- (LR) or high-responders (HR), where LRs are in the low locomotor range while HRs belong to the high locomotor range, is significant in that HRs show higher activity in mesencephalic dopaminergic projection neurons, and also show a higher propensity to self-administer psychostimulants and other drugs of abuse compared with LRs. In this study, we examined the neurobiological basis of dopaminergic hyperactivity by comparing in HRs and LRs the steady-state differences in regulatory inputs to mesencephalic (substantia nigra and ventral tegmental area: VTA) dopaminergic neurons. In particular, using in situ hybridization, we studied levels of mRNA for tyrosine hydroxylase (TH) and cholecystokinin (CCK) in the mesencephalon, and for preprodynorphin (DYN), preproenkephalin (PPE), and preprotachykinin (PPT) in the striatum and nucleus accumbens (Acb). We also evaluated TH levels by radioimmunocytochemistry (TH-RIC) in striatal, accumbal and mesencephalic regions. HRs versus LRs had lower levels of neurochemicals belonging to the intrinsic inhibitory input to dopaminergic neurons in the VTA, e.g. lower TH-RIC (–25%) and CCK-mRNA (–48%). In contrast, HRs showed higher levels of parameters belonging to extrinsic facilitating inputs, e.g. higher PPE-mRNA (+ 37%). In addition, HRs had higher DYN-mRNA in Acb (+ 61%), which has been shown to be positively correlated with higher dopaminergic activity. These results enhance our knowledge of the neurobiological correlates of individual rats' propensities to develop drug-intake and provide some putative mechanisms for the dopaminergic hyperactivity that characterizes drug-prone animals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1998.00321.x
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  • 7
    Electronic Resource
    Electronic Resource
    The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens (2002)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 16 (2002), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently from peripheral sources. Clinical studies in humans have associated these hormones with depression and postpartum mood disorders. In rodents, allopregnanolone (AlloP) has been shown to have anxiolytic and rewarding properties. These observations suggest that neurosteroids could interact with mood and motivation. However, the possible neural substrates of these effects remain unknown. In this report, we have studied the action of AlloP on the activity of the mesencephalic dopaminergic (DA) projection to the nucleus accumbens, which is considered one of the biological substrates of motivation and reward. This study was conducted by measuring extracellular concentrations of dopamine (DA) in the nucleus accumbens by means of microdialysis in freely moving rats. We studied both the direct effect of AlloP and the influence of this hormone on the DA response to an injection of morphine. AlloP dose-dependently increased the release of DA in the nucleus accumbens. Furthermore, this hormone doubled the DA response to morphine. These effects were observed for AlloP doses of 50 and 100 pmol injected intracerebroventricularly. These results suggest that the stimulatory effect of AlloP on DA could mediate some of the behavioural effects of neurosteroids and, in particular, the interaction of these hormones with mood and motivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2002.02084.x
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  • 8
    Electronic Resource
    Electronic Resource
    The dopaminergic hyper-responsiveness of the shell of the nucleus accumbens is hormone-dependent (2000)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 12 (2000), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The dopaminergic projection to the shell of the nucleus accumbens is the most reactive to stress, reward and drugs of abuse and this subregion of the nucleus accumbens is also considered a target of therapeutic effects of atypical antipsychotic drugs (APD). In this report we show, by means of in vivo microdialysis and Fos immunohistochemistry, that the hyper-responsiveness which characterizes the dopaminergic transmission to the shell is dependent on glucocorticoid hormones. In Sprague-Dawley rats, after suppression of endogenous glucocorticoids by adrenalectomy, extracellular dopamine levels selectively decreased in the shell, whilst they remained unchanged in the core. This effect was observed in basal conditions, after a mild stress (vehicle injection), as well as after subcutaneous administration of morphine (2 mg/kg, s.c.) or intraperitoneal injection of cocaine (15 mg/kg, i.p.). The decrease in dopamine observed in the shell had a postsynaptic impact, as shown by less induction of Fos-like proteins selectively in the shell in response to cocaine. However, the induction of Fos-like proteins by the full D1 agonist SKF82958 (1.5 mg/kg, i.p.) remained unchanged after adrenalectomy, suggesting that the changes in Fos expression after cocaine injection were likely to depend on changes in extracellular dopamine levels rather than on changes in postsynaptic sensitivity to dopamine. The effects of adrenalectomy were glucocorticoid-specific given that they were prevented by corticosterone treatment. This anatomical specificity in the control of neuronal activity by a hormonal input highlights the role of steroid hormones in shaping the functional activity of the brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00996.x
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  • 9
    Electronic Resource
    Electronic Resource
    Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat (1999)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: There is growing evidence that stress during prenatal and postnatal periods of life can modify adaptive capacities in adulthoods. The hypothalamo–pituitary–adrenal axis may mediate an animal’s responses to perinatal stressful events and thus serve as a neurobiological substrate of the behavioural consequences of these early events. However, little is known about the long-term effects of prenatal stressors throughout the entire life of the animals. The focus of the present study was to examine the long-term influences of a prenatal and postnatal stress on glucocorticoid secretion and cognitive performance. Prenatal stress of rat dams during the last week of pregnancy and postnatal daily handling of rat pups during the first 3 weeks of life were used as stressors. The long-term effects of these manipulations were analysed using a longitudinal approach throughout the entire life of the animals, and were repeatedly tested in adulthood (4–7 months), middle age (13–16 months) and in later life (20–24 months). The study demonstrated that prenatal stress and postnatal handling induced opposite effects on both glucocorticoid secretion and cognitive performance. Prenatal stress accelerated the age-related hypothalamo–pituitary–adrenal axis dysfunctions; indeed, circulating glucocorticoids levels of prenatally stressed middle-aged animals are similar to old control ones, and also induced cognitive impairments. In contrast, postnatal handling protected from the age-related neuroendocrine and behavioural alterations. These results show that the altered glucocorticoid secretion induced by early environmental manipulations is primary to the cognitive alterations observed only later in life and could be one cause of age-related memory deficits.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1999.00705.x
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  • 10
    Electronic Resource
    Electronic Resource
    The neurosteroid pregnenolone sulphate increases dopamine release and the dopaminergic response to morphine in the rat nucleus accumbens (1999)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 11 (1999), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Neurosteroids are a subclass of steroids that can be synthesized in the central nervous system independently of peripheral sources. Clinical studies in humans have associated some of these hormones with a generic sensation of ‘well-being’ and with pathologies such as depression. In rodents, the neurosteroid pregnenolone sulphate (Preg-S) has been shown to present antidepressant-like effects. These observations suggest that neurosteroids could interact with reward-related processes, mood and motivation. However, the possible neural substrates of such an effect remain unclear. In this report, we studied the action of Preg-S on the activity of the mesencephalic dopaminergic projection to the nucleus accumbens which is considered one of the biological substrates of motivation and reward. Both the direct effect of Preg-S and the influence of this hormone on the dopaminergic response to the pharmacological reward provided by the opiate morphine, were studied by means of microdialysis. Pregnenolone sulphate dose-dependently increased dopamine release in the nucleus accumbens. Furthermore, this hormone doubled the dopaminergic response to morphine. These effects were observed for Preg-S doses of 100, 200, and 400 pmol injected intracerebroventricularly. The stimulant effect of Preg-S on dopamine could mediate some of the behavioural effects of neurosteroids and in particular the interaction of these hormones with mood and motivation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.1999.00816.x
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