S Sarre

Publications (53)138.08 Total impact

• Source

  Available from: Luc LR Int Panis

  Dataset: supplementary files for ResearchGate

  I Bos, P De Boever, L Int Panis, S Sarre, R Meeusen
• Source

  Available from: Patrick De Boever

  Article: Negative effects of ultrafine particle exposure during forced exercise on the expression of Brain-Derived Neurotrophic Factor in the hippocampus of rats.

  I Bos, P De Boever, L Int Panis, S Sarre, R Meeusen
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  ABSTRACT: Exercise improves cognitive function, and Brain-Derived Neurotrophic Factor (BDNF) plays a key role in this process. We recently reported that particulate matter (PM) exposure negatively contributed to the exercise-induced increase in human serum BDNF concentration. Furthermore, PM exposure is associated with neuroinflammation and cognitive decline. The aim of this study was to investigate the effect of exposure to ultrafine particles (UFP) during a single bout of forced exercise on the expression of inflammatory (IL1α, IL1β, TNF, IL6, NOS2, NOS3) and oxidative stress (NFE2L2)-related genes, as well as BDNF in the brain of rats. Four groups (n=6/group) of Wistar rats were exposed for 90min to one of the following exposure regimes: UFP+exercise, UFP+rest, ambient air+exercise, ambient air+rest (control). Hippocampus, olfactory bulb and prefrontal cortex were collected 24h after exposure. Gene expression changes were analyzed with real-time PCR. In the condition ambient air+exercise, hippocampal expression of BDNF and NFE2L2 was up-regulated, while the expression of IL1α and NOS3 in the prefrontal cortex and IL1α in the olfactory bulb was down-regulated compared to the control. In contrast, gene expression in the condition UFP+exercise did not differ from the control. In the condition UFP+rest, hippocampal expression of NFE2L2 was down-regulated and there was a trend toward down-regulation of BDNF expression compared to the control. This study shows a negative effect of UFP exposure on the exercise-induced up-regulation of BDNF gene expression in the hippocampus of rats.
  Neuroscience 08/2012; 223:131-9. · 3.38 Impact Factor
• Article: Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in Parkinson disease.

  D Deleu, P Jacob, P Chand, S Sarre, A Colwell
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  ABSTRACT: The authors studied the acute effect of caffeine on the levodopa pharmacokinetics and pharmacodynamics in 12 patients with idiopathic Parkinson disease. This double-blind, randomized, crossover study revealed that caffeine shortened the maximal plasma concentration of levodopa, decreased the latency to levodopa walking and tapping motor response, and increased the magnitude of walking response. Caffeine administered before levodopa may improve its pharmacokinetics in some parkinsonian patients.
  Neurology 10/2006; 67(5):897-9. · 8.31 Impact Factor
• Article: Postischemic mild hypothermia reduces neurotransmitter release and astroglial cell proliferation during reperfusion after asphyxial cardiac arrest in rats.

  S Hachimi-Idrissi, A Van Hemelrijck, A Michotte, I Smolders, S Sarre, G Ebinger, L Huyghens, Y Michotte
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  ABSTRACT: The present study investigated whether postischemic mild hypothermia attenuates the ischemia-induced striatal glutamate (GLU) and dopamine (DA) release, as well as astroglial cell proliferation in the brain. Anesthetized rats were exposed to 8 min of asphyxiation, including 5 min of cardiac arrest. The cardiac arrest was reversed to restoration of spontaneous circulation (ROSC), by brief external heart massage and ventilation within a period of 2 min. After the insult and during reperfusion, the extracellular glutamate and dopamine overflow increased to, respectively, 3000% and 5000% compared with the baseline values in the normothermic group and resulted in brain damage, ischemic neurons and gliosis. However, when hypothermia was induced for a period of 60 min after the insult and restoration of spontaneous circulation, the glutamate and dopamine overflows were not significantly different from that in the sham group. Histological analysis of the brain showed that postischemic mild hypothermia reduced brain damage, ischemic neurons, as well as astroglial cell proliferation. Thus, postischemic mild hypothermia reduces the excitotoxic process, brain damage, as well as astroglial cell proliferation during reperfusion. Moreover, these results emphasize the trigger effect of dopamine on the excitotoxic pathway.
  Brain Research 10/2004; 1019(1-2):217-25. · 2.73 Impact Factor
• Source

  Available from: sarb.be

  Article: Formalin-induced spinal glutamate release in freely moving rats: comparison of two spinal microdialysis approaches.

  L Shi, I Smolders, S Sarre, Y Michotte, M Zizi, F Camu
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  ABSTRACT: Two different spinal microdialysis approaches using either a linear tissue probe (LM-3) or a loop probe were explored on freely-moving rats to investigate the basal and formalin-evoked release of glutamate (Glu) in the spinal dorsal horn or in the cerebrospinal fluid (CSF). Adult male Wistar rats were implanted either with a LM-3 probe transversely through the spinal dorsal horn or with a loop probe in the CSF. After 24 hours recovery, microdialysis was initiated with perfusion of modified Ringer's solution at a flow rate of 5 microliters/min and the basal Glu concentrations were sampled for 1 hour. The effects of altering the microdialysis flow rate and perfusion solution on basal Glu release were next investigated. Following the injection of 50 microliters of formalin 5% into the hind paw, 10-min samples were collected for 90 min. The baseline levels of Glu were 0.82 +/- 0.09 microM with LM-3 probes and 5.96 +/- 0.22 microM with the loop probes. Decreasing the flow rate from 5 to 2 microliters/min increased extracellular Glu concentrations by 222.7 +/- 7.3%, whereas perfusion with artificial CSF reduced baseline Glu by 61.5 +/- 9.5% with LM-3 probes. Injection of formalin induced a short-lasting but significant increase of Glu with a similar profile and time course when using either of the microdialysis approaches. In conclusion, microdialysis in the dorsal horn or in the CSF are both effective techniques to assess the alterations in Glu release following peripheral nociceptive input. The loop probe technique in CSF is more reproducible for routine investigation of drug effects, whereas the microdialysis of the dorsal horn provides a useful tool to precisely locate where the release of the neurotransmitters occurs.
  Acta anaesthesiologica Belgica 02/2004; 55(1):43-8.
• Article: Effects of venlafaxine on extracellular 5-HT, dopamine and noradrenaline in the hippocampus and on peripheral hormone concentrations in the rat in vivo.

  M F Piacentini, R Clinckers, R Meeusen, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: The purpose of the present study was to study the effect of an acute dose of the serotonin (5-HT) - noradrenaline (NA) reuptake inhibitor venlafaxine on extracellular concentrations of 5-HT, NA and dopamine (DA) in the hippocampus and on the peripheral hormone concentrations in freely moving rats. Blood obtained from a catheter placed in the vena femoralis was analyzed for adrenocorticotropin (ACTH), beta-endorphins, prolactin (PRL), growth hormone (GH) and cortisol. Collections are referred to pre and post injection of 20 mg/kg of venlafaxine. Extracellular hippocampal NA and 5-HT as determined with in vivo microdialysis increased significantly after drug injection. PRL and ACTH were significantly affected by the drug. At the selected dose venlafaxine is able to increase the release of 5-HT but also of NA in rat hippocampus. Due to the dual reuptake properties of the drug and the functional interconnection of the NA and the 5-HT systems, the observed effects on peripheral hormones are possibly mediated by a combined action of these 2 systems.
  Life Sciences 10/2003; 73(19):2433-42. · 2.53 Impact Factor
• Article: Effect of bupropion on hippocampal neurotransmitters and on peripheral hormonal concentrations in the rat.

  M F Piacentini, R Clinckers, R Meeusen, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: The purpose of the present study was to administer an acute dose of the dual dopamine norepinephrine reuptake blocker bupropion in freely moving rats and to monitor the extracellular neurotransmitter concentrations in the hippocampus via in vivo microdialysis and the peripheral hormonal concentrations via catheterization. A microdialysis probe was inserted in the hippocampus, and samples for serotonin, dopamine, and norepinephrine were collected every 20 min before and after the injection of 17 mg/kg of bupropion, for a total sampling time of 180 min. A catheter was placed in the vena femoralis of the second group of rats, and blood samples were collected before and after bupropion injection for quantification of growth hormone, prolactin, corticosterone, adrenocorticotropin hormone, and beta-endorphins. All neurotransmitter levels (dopamine, norepinephrine, and serotonin) significantly increased after bupropion injection. This was accompanied by a significant decrease in prolactin concentrations, whereas the other hormones showed no statistically significant variation. It can, therefore, be concluded that, although bupropion has dual reuptake proprieties, the observed effects both at the central and at the peripheral level seem to be ruled by the dopaminergic system.
  Journal of Applied Physiology 09/2003; 95(2):652-6. · 3.75 Impact Factor
• Article: Effects of dietary sucrose on hippocampal serotonin release: a microdialysis study in the freely-moving rat.

  I Smolders, J V Loo, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: The effects of dietary supplementation with either sucrose or starch (50 g/kg regular food for 2 weeks) on central 5-hydroxytryptamine (5HT; serotonin) release were investigated in freely-moving rats. It has been suggested that the amount of transmitter that serotoninergic neurons release might be altered by food intake. We monitored the effects of sucrose and starch on concentrations of extracellular 5HT, its metabolite 5-hydroxyindoleacetic acid (5HIAA), gamma-aminobutyric acid (GABA) and dopamine in the hippocampus, using in vivo microdialysis. The major finding was that baseline levels of extracellular hippocampal 5HT in rats with ad libitum access to food supplemented with sucrose were significantly higher compared with the starch control group. We then verified that sucrose supplementation affected the potency of S(+)fenfluramine to increase hippocampal 5HT levels. In both groups of rats, acute intraperitoneal injection (1 mg/kg) of this anorectic drug induced a response curve of the extracellular hippocampal 5HT levels, with a shape that corresponded with earlier data for different brain areas often using up to 10-fold higher doses of S(+)fenfluramine. Nevertheless, we showed that throughout the experiment the absolute values of the sucrose response curve remained higher than in the starch group. On the other hand, S(+)fenfluramine exerted longer lasting effects in the starch group, as compared with the sucrose group. Significant decreases in levels of extracellular hippocampal 5HIAA levels following S(+)fenfluramine administration were simultaneously observed. A practical implication of the present findings is that dietary sucrose may bias the results of studies investigating brain serotoninergic mechanisms and the effects of (anorectic) drugs interacting with 5HT systems in the hippocampus.
  British Journal Of Nutrition 09/2001; 86(2):151-5. · 3.01 Impact Factor
• Article: Benserazide decreases central AADC activity, extracellular dopamine levels and levodopa decarboxylation in striatum of the rat.

  N Jonkers, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: In Parkinsonian patients treated with levodopa, peripheral decarboxylase inhibitors like carbidopa and benserazide are used to increase the central availability of levodopa. In experimental animal studies, this clinical situation is mimicked. However, at the dose used in many animal studies, both benserazide and carbidopa pass the blood brain barrier. In this study, we investigated to what extent their presence in brain inhibits striatal aromatic amino acid decarboxylase activity. At 50 mg/kg i.p., both carbidopa and benserazide decreased striatal decarboxylase activity. At 10 mg/kg i.p., only benserazide decreased the enzyme activity, but this did not change extracellular dopamine in striatum and allowed dopamine levels to increase after levodopa administration. In contrast, the inhibition of central decarboxylase activity by 50 mg/kg benserazide decreased striatal dopamine levels and prevented the levodopa-induced increase. Therefore, it is important to carefully consider the dose of the peripheral decarboxylase inhibitor used when the central effects of levodopa are studied.
  Acta Neurovegetativa 02/2001; 108(5):559-70. · 2.73 Impact Factor
• Article: The effects of LY393613, nimodipine and verapamil, in focal cerebral ischaemia.

  L Bogaert, M J O'Neill, J Moonen, S Sarre, I Smolders, G Ebinger, Y Michotte
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  ABSTRACT: This study evaluates the effects of N-(2-[bis (4-fluorophenyl)methoxy]ethyl)-1-butanamine hydrochloride (LY393613), a novel neuronal (N/P/Q-type) Ca(2+) channel blocker, in ischaemia. For comparison, two commonly used L-type Ca(2+) channel blockers; nimodipine and verapamil were also evaluated. Ischaemia was induced in freely moving rats by micro-injection of endothelin-1 near the middle cerebral artery. In vivo microdialysis, laser Doppler flowmetry and histology were used to monitor ischaemia. Administration of LY393613, before and after the insult, attenuated the ischaemia-induced glutamate release, but not the dopamine release. Both nimodipine and verapamil failed to affect transmitter releases significantly, when administered post-occlusion. None of the compounds tested, produced any significant change in striatal blood flow. Histology showed that ischaemic damage was significantly less in LY393613 pre-treated rats. In conclusion, LY393613, a neuronal N/P/Q-Ca(2+) channel blocker, can attenuate ischaemic brain damage. The protective mechanism appears to be mainly the attenuation of the ischaemia-induced glutamate release, rather than its effect on cerebral hemodynamics.
  European Journal of Pharmacology 02/2001; 411(1-2):71-83. · 2.52 Impact Factor
• Article: Neurochemical changes and laser Doppler flowmetry in the endothelin-1 rat model for focal cerebral ischemia.

  L Bogaert, D Scheller, J Moonen, S Sarre, I Smolders, G Ebinger, Y Michotte
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  ABSTRACT: Generalized neurotransmitter overflow into the extracellular space, after cerebral ischemia, has been suggested to contribute to subsequent neuronal death. This study aims to investigate the striatal release of the neurotransmitters dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) by means of microdialysis, in a rat model for focal transient cerebral ischemia. Ischemia was induced by the application of 120 pmol endothelin-1 (Et-1), adjacent to the middle cerebral artery (MCA) in freely moving rats. Ischemia produced a large increase in extracellular striatal DA concentrations (2400%), Glu (5500%) and GABA (800%) concentrations. Laser Doppler flowmetry in anaesthetized rats, indicated that the blood flow within the striatum decreased by 75+/-11%. The period of sustained drop of blood flow, was dose-dependently related to the concentration Et-1 injected. Histological analysis of brain slices, taken from anaesthetized and conscious animals, indicated a 500 pmol dose of Et-1 was required to produce a similar infarct in anaesthetized rats to a 120 pmol dose of Et-1 in freely moving rats. The immediate drop in striatal blood flow, and the prompt increase of extracellular DA, after the micro-application of Et-1, were quite striking. This suggests that the DA release, rather than the Glu overflow may be the primary event initiating the cascade of processes ultimately leading to cell death and neurological deficits.
  Brain Research 01/2001; 887(2):266-75. · 2.73 Impact Factor
• Article: MK801 influences L-DOPA-induced dopamine release in intact and hemi-parkinson rats.

  N Jonkers, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: In vivo microdialysis was used to investigate the influence of dizocilpine (MK801) on basal and levodopa (L-DOPA)-induced extracellular dopamine levels in striatum and substantia nigra of intact and 6-hydroxydopamine-lesioned rats. In lesioned rats, extracellular dopamine was decreased in striatum but not in substantia nigra. L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i. p.) increased the dopamine levels in striatum and substantia nigra of intact and dopamine-depleted rats. This increase was significantly higher in dopamine-depleted compared to intact striatum. Pretreatment with MK801 (0.1 and 1.0 mg/kg i.p.) dose-dependently attenuated the L-DOPA-induced dopamine release in substantia nigra of intact rats. In dopamine-depleted striatum, MK801 enhanced L-DOPA-induced dopamine release. The present results indicate that the influence of MK801 on L-DOPA-induced dopamine release in striatum and substantia nigra depends on the integrity of the nigrostriatal pathway. In Parkinson's disease, NMDA receptor antagonists could be beneficial by enhancing the therapeutic efficacy of L-DOPA at the level of the striatum.
  European Journal of Pharmacology 12/2000; 407(3):281-91. · 2.52 Impact Factor
• Article: Muscarinic antagonists in substantia nigra influence the decarboxylation of L-dopa in striatum.

  P Izurieta-Sánchez, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: This study was designed to investigate whether anticholinergic drugs acting at the level of the substantia nigra can affect basal extracellular dopamine concentrations and the levodopa (L-dopa)-induced increases in dopamine levels in the striatum. Dual probe in vivo microdialysis in freely moving rats was used. One microdialysis probe was implanted in the substantia nigra and the other in the ipsilateral striatum. Muscarinic receptor antagonists were perfused into the substantia nigra and changes in neurotransmitter levels in the substantia nigra and at the axon terminals in the striatum were monitored simultaneously. Nigral perfusion of the non-selective muscarinic receptor antagonist trihexyphenidyl (1 mM) produced an increase in extracellular dopamine and gamma-aminobutyric acid (GABA) levels in the substantia nigra. Perfusion with the muscarinic M(1) receptor antagonist telenzepine (0.1 microM) produced a significant decrease in nigral dopamine and GABA levels in the substantia nigra. The muscarinic M(2) receptor antagonist methoctramine (75 microM) produced an increase in dopamine levels in the substantia nigra. No significant changes in nigral extracellular GABA levels were observed. The L-dopa-induced increases in extracellular dopamine levels in the striatum were clearly attenuated under nigral perfusion of these drugs. This in vivo study demonstrates that anticholinergic drugs perfused at the level of the substantia nigra can modulate dopamine and GABA levels and attenuate the L-dopa decarboxylation in the striatum, possibly via modulation of the nigrostriatal dopaminergic system. We add further evidence that the substantia nigra is an important site of action of antimuscarinic drugs. The attenuation of L-dopa-induced dopamine release in the striatum exerted by nigral perfusion of these antimuscarinic drugs is probably mediated via different mechanisms. This attenuation is regarded as a beneficial effect of the muscarinic antagonists as adjuncts to L-dopa in Parkinson's disease treatment. We postulate that drugs that enhance dopamine release, after L-dopa administration, in a less extreme way than L-dopa administered on its own could prevent further neurodegeneration and dyskinesias thought to result from extremely high extracellular dopamine levels following L-dopa treatment.
  European Journal of Pharmacology 08/2000; 399(2-3):151-60. · 2.52 Impact Factor
• Article: Neostigmine influences the L-dopa-induced extracellular dopamine levels in the striatum.

  P Izurieta-Sánchez, N Jonkers, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: Using in vivo microdialysis in freely moving rats, we show that the addition to the dialysis perfusion fluid of the acetylcholinesterase inhibitor neostigmine influences the decarboxylation of levodopa (L-dopa). Continuous perfusion of neostigmine (10, 50 and 100 nM) in striatum attenuated the L-dopa-induced dopamine release in a dose-dependent manner. This effect suggests that changes in magnitude of drug responses may occur when an acetylcholinesterase inhibitor is included in the perfusion solution. Results obtained under these circumstances should be carefully interpreted concerning the pharmacological effects of other drugs when used concomitantly with neostigmine.
  Brain Research 03/2000; 856(1-2):250-3. · 2.73 Impact Factor
• Article: Serotonin reuptake inhibition by citalopram in rat strains differing for their emotionality.

  F Pollier, S Sarre, S Aguerre, G Ebinger, P Mormède, Y Michotte, F Chaouloff
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  ABSTRACT: Acute administration of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram (1-10 mg/kg, i.p. 1 h before an elevated plus-maze test), to Spontaneously Hypertensive rats (SHRs), Lewis (LEW) rats, and Wistar-Kyoto (WKY) rats, i.e., rat strains differing for their emotionality, promoted anxiety, and/or hypoactivity, except in WKY rats. In the three strains, such a pretreatment increased central 5-HT levels and/or decreased 5-hydroxyindoleacetic acid levels. Hippocampal, but not midbrain or striatal, [3H]citalopram binding at 5-HT transporters was lower in WKY rats than in SHRs. However, neither [3H]5-HT reuptake kinetics nor the potencies of citalopram (1-1000 nM) to inhibit [3H]5-HT reuptake into hippocampal and striatal synaptosomes differed between strains. This was confirmed in vivo by means of microdialysis in the hippocampus of freely moving rats. Thus, although LEW rats displayed a 3-4 fold higher baseline level of extracellular 5-HT in the hippocampus, compared with SHRs and WKY rats, local perfusion with 1 microM citalopram promoted relative increases in extracellular 5-HT levels over baseline that were similar in all strains. Lastly, acute i.p. administration of 3.3 mg/kg citalopram (1 h beforehand) decreased to similar extents [3H]5-HT reuptake into hippocampal synaptosomes from SHRs and WKY rats. This study indicates that genetic differences in the behavioural responses to SSRIs may involve 5-HT transporter-independent mechanisms.
  Neuropsychopharmacology 02/2000; 22(1):64-76. · 7.99 Impact Factor
• Article: Effect of trihexyphenidyl, a non-selective antimuscarinic drug, on decarboxylation of L-dopa in hemi-Parkinson rats.

  P Izurieta-Sánchez, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: In vivo microdialysis was used to study the effect of the non-selective muscarinic antagonist, trihexyphenidyl, on the decarboxylation of levodopa (L-dopa) in the striatum of hemi-Parkinson rats. In normal rats, continuous perfusion of trihexyphenidyl (1 mM) via the microdialysis probe induced a significant increase in striatal dopamine release, followed by a decrease to below baseline values. A similar effect was observed, though less pronounced, in denervated striatum of rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. In these hemi-Parkinson rats, continuous striatal perfusion of trihexyphenidyl had no effect on the biotransformation of locally applied L-dopa (2 microM for 20 min) to dopamine in either intact or denervated striatum. However, systemic administration of trihexyphenidyl (1.5 mg/kg i.p.) produced an attenuation of the L- dopa-induced dopamine release in the intact striatum (contralateral to the lesion) of hemi-Parkinson rats. This effect was absent in the denervated striatum of these animals. We confirmed that L-dopa induces an increase in striatal dopamine output which is influenced by the severity of the dopaminergic denervation. The absence of an effect of trihexyphenidyl locally applied in the striatum, on biotransformation of L-dopa suggests that the site of action of antimuscarinic drugs may not be in the striatum and, therefore, remains unclear. The mechanism of action of these drugs is not well understood but appears more complicated than previously thought.
  European Journal of Pharmacology 08/1998; 353(1):33-42. · 2.52 Impact Factor
• Article: Dopaminergic regulation of serotonin release in the substantia nigra of the freely moving rat using microdialysis.

  K Thorré, S Sarre, I Smolders, G Ebinger, Y Michotte
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  ABSTRACT: The functional regulation by dopamine (DA) receptors of serotonin (5-HT) release from the rat substantia nigra (SN) was investigated using in vivo microdialysis. A D1- and D2-receptor-mediated inhibition of nigral 5-HT release was demonstrated in this study. Continuous administration of the D1-receptor agonist CY 208243 (10 microM) through the probe did not alter extracellular DA nor 5-HT from the SN, whereas intranigral administration of the D1-receptor antagonist SCH-23390 HCl (10 microM) significantly increased both DA (to 214%) and 5-HT release (to 168%) from the SN. Co-perfusion of the D1-receptor agonist and antagonist did not change nigral DA nor 5-HT release compared to perfusion of the antagonist alone. The continuous intranigral perfusion of the D2-receptor agonist, (-)-quinpirole HCl (1 microM) significantly decreased both DA ad 5-HT release to 71% and 78%, respectively. These decreases were abolished when the D2-receptor antagonist S(-)-sulpiride (10 microM) and the D2-receptor agonist (-)-quinpirole HCl (1 microM) were co-perfused. In contrast, the intranigral perfusion of the DA precursor, L-DOPA (5 microM; 1 h), significantly increased nigral and striatal 5-HT release to 202% and 155%, respectively. This enhanced nigral 5-HT release might not be receptor-mediated. The results of the present study suggest a D1 and D2 regulation of nigral 5-HT release, either directly mediated by DA receptors on nigral 5-HT terminals or indirectly by nigral GABA, Glu or Asp. Alternatively, the observed DA-5HT-interaction in the SN might not reflect a local interaction but might involve an interaction at the level of the serotonin cell body region, the dorsal raphe nuclei (DRN).
  Brain Research 07/1998; 796(1-2):107-16. · 2.73 Impact Factor
• Article: Biotransformation of L-DOPA to dopamine in the substantia nigra of freely moving rats: effect of dopamine receptor agonists and antagonists.

  S Sarre, D Vandeneede, G Ebinger, Y Michotte
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  ABSTRACT: We investigated the effects of continuous intranigral perfusion of dopamine D1 and D2 receptor agonists and antagonists on the biotransformation of locally applied L-DOPA to dopamine in the substantia nigra of freely moving rats by means of in vivo microdialysis. The "dual-probe" mode was used to monitor simultaneously changes in extracellular dopamine levels in the substantia nigra and the ipsilateral striatum. Intranigral perfusion of 10 microM L-DOPA for 20 min induced a significant 180-fold increase in extracellular nigral dopamine level. No effect of the intranigral L-DOPA administration was observed on dopamine levels in the ipsilateral striatum, suggesting a tight control of extracellular dopamine in the striatum after enhanced nigral dopamine levels. Continuous nigral infusion with the D1 receptor agonist CY 208243 (10 microM) and with the D2 receptor agonist quinpirole at 10 microM (a nonselective concentration) attenuated the L-DOPA-induced increase in dopamine in the substantia nigra by 85 and 75%, respectively. However, perfusion of the substantia nigra with a lower concentration of quinpirole (1 microM) and the D1 antagonist SCH 23390 (10 microM) did not affect the nigral L-DOPA biotransformation. The D2 antagonist (-)-sulpiride (10 microM) also attenuated the L-DOPA-induced dopamine release in the substantia nigra to approximately 10% of that of the control experiments. We confirm that there is an important biotransformation of L-DOPA to dopamine in the substantia nigra. The high concentrations of dopamine formed after L-DOPA administration may be the cause of dyskinesias or further oxidative stress in Parkinson's disease. Simultaneous administration of D1 receptor agonists with L-DOPA attenuates the biotransformation of L-DOPA to dopamine in the substantia nigra. The observed effects could occur via changes in nigral GABA release that in turn influence the firing rate of the nigral dopaminergic neurons.
  Journal of Neurochemistry 05/1998; 70(4):1730-9. · 4.06 Impact Factor
• Article: Differential effects of restraint stress on hippocampal 5-HT metabolism and extracellular levels of 5-HT in streptozotocin-diabetic rats.

  K Thorré, F Chaouloff, S Sarre, R Meeusen, G Ebinger, Y Michotte
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  ABSTRACT: Streptozotocin (STZ)-elicited diabetes reduces central serotonin (5-hydroxytryptamine, 5-HT) synthesis/metabolism, but whether this reduction leads to decreased release of 5-HT has only scarcely been investigated. We have thus analysed the impact of STZ diabetes on hippocampal extracellular 5-HT levels both under basal conditions and during restraint stress, a procedure known to stimulate hippocampal 5-HT synthesis/metabolism and release. The pretreatment with STZ (3 weeks beforehand) and the 1 h restraint session respectively decreased and increased hippocampal 5-HT metabolism, as assessed by tissue analysis of 5-HT and 5-hydroxyindoleacetic acid. On the other hand, hippocampal microdialysis revealed no difference in basal levels of extracellular 5-HT levels in (conscious) vehicle- and STZ-pretreated rats, but a differential effect of restraint. Thus, extracellular 5-HT levels increased throughout restraint (maximal increase: 194%) in vehicle-, but not in STZ-pretreated rats. In the latter rat group, plasma corticosterone levels were, however, increased, thus indicating a significant aversiveness to stress. Lastly, because anxiety-related behaviours may be affected by hippocampal serotonergic systems, resting and restrained vehicle- and STZ-pretreated rats were compared (immediately after stress) in an elevated plus-maze of anxiety. Pretreatment with STZ reduced the percent number of open arm entries and the number of closed arm entries, indicating increased anxiety and reduced locomotor activity, respectively. Restraint tended to increase anxiety-related behaviours in all rats, but this trend never reached significance. Our results confirm that gross analyses of 5-HT metabolism do not yield information on 5-HT release, and suggest that the prevalence of diabetes among patients suffering affective disorders could be related to the lack of hippocampal serotonergic response to aversive stimuli.
  Brain Research 11/1997; 772(1-2):209-16. · 2.73 Impact Factor
• Article: Characterization of the extracellular serotonin release in the substantia nigra of the freely moving rat using microdialysis.

  K Thorré, S Sarre, G Ebinger, Y Michotte
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  ABSTRACT: The characteristics of the serotonin release were investigated in the substantia nigra (SN) of the freely moving rat using microdialysis. We also examined whether the delay between surgery and microdialysis experiments might influence these characteristics by implanting rats with a guide cannula 1 or 2 days prior to microdialysis experiments. In the first group, the tissue was not punctured until the microdialysis probe was inserted the evening before the experiment. In the second group, the nigral tissue was punctured with an extended obturator which was then replaced by a microdialysis probe the evening before the experiment. After administration of 60 mM K+ a more pronounced increase in serotonin was observed in the first group (260%) compared to the second group (159%). Calcium-free and tetrodotoxin (TTX, a sodium channel blocker) (1 microM) perfusion reduced extracellular serotonin to respectively 77% and 80% in the first group and 70% and 64% in the second group. These results suggest that vesicular release of nigral serotonin only occurs partially in this region and that minimizing the damage caused by implantation of the probe results only in 10% more vesicular release of serotonin. However, blockade of the serotonin reuptake carrier caused more TTX sensitivity of the serotonin release. Also, stimulation of the dorsal raphe by locally perfusing 60 mM K+ decreased serotonin in the SN, confirming the anatomical and functional link between both areas.
  Brain Research 11/1997; 772(1-2):29-36. · 2.73 Impact Factor