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See detailDifferential taurine responsiveness to ethanol in high- and low-alcohol sensitive rats : a brain microdialysis study
Quertemont, Etienne ULg; Linotte, Sylvie; De Witte, Philippe

in European Journal of Pharmacology (2002), 444(3), 143-150

Several microdialysis studies have investigated the effects of acute ethanol on extracellular amino acids in various rat brain regions, However, these studies led to conflicting results, suggesting that ... [more ▼]

Several microdialysis studies have investigated the effects of acute ethanol on extracellular amino acids in various rat brain regions, However, these studies led to conflicting results, suggesting that individual differences between rat strains and lines may play an important role. In the present study, high-alcohol sensitive (HAS) and low-alcohol sensitive (LAS) rats were used to investigate the possible relationship between ethanol sensitivity and the concentrations of extracellular amino acids in the nucleus accumbens. Several groups of HAS and LAS rats were injected with either saline or ethanol (1.0, 2.0 or 3.0 g/kg, i.p.) and the concentrations of amino acids in the nucleus accumbens microdialysates were assayed by electrochemical detection. Acute ethanol induced a dose-dependent increase in extracellular taurine concentrations. However, this increase was significantly reduced at 2,0 and 3.0 g,,kg ethanol in HAS rats relative to LAS rats. Since the biological functions of taurine suggest its implication in the reduction of ethanol adverse effects, a higher increase in taurine concentrations may contribute to the lower ethanol sensitivity of LAS rats. Although 2.0 and 3.0 g/kg ethanol did not affect extracellular glutamate concentrations, a significant increase in glutamate was observed after 1.0 g/kg ethanol to HAS rats but not to LAS rats. Such an effect remains unexplained but suggests that discrepancies between the results of previous microdialysate studies may be related to differences in the ethanol sensitivities of various rat strains. (C) 2002 Elsevier Science B.V All rights reserved. [less ▲]

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See detailRole of acetaldehyde in the discriminative stimulus effects of ethanol
Quertemont, Etienne ULg; Grant, Kathleen A

in Alcoholism, Clinical & Experimental Research (2002), 26(6), 812-817

Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase ... [more ▼]

Background: Acetaldehyde has been suggested to mediate some of the effects of ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain after ethanol administration. The catalase inhibitor 3-amino-1,2,4-triazole (AT) reduces the production of acetaldehyde, and AT administration can reduce a number of ethanol-induced behavioral effects; this suggests the involvement of acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating the discriminative stimulus effects of ethanol remains unclear. Methods: The contribution of acetaldehyde to the discriminative stimulus effects of ethanol was investigated by use of a two-lever drug discrimination paradigm with food reinforcement. Male Long-Evans rats were trained to discriminate water from either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with ethanol (0 –2.5 g/kg by gavage) and acetaldehyde (0–300 mg/kg intraperitoneally). A cumulative dose-response procedure was then used to investigate the effects of pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol discrimination. Results: Acetaldehyde up to doses that decreased response rates (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or 2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose-response curves for ethanol discrimination. Conclusions: These results show that exogenous acetaldehyde administration does not produce discriminative stimulus effects that are similar to those of ethanol. Also, pretreatment with the catalase inhibitor did not affect the dose-response curve for ethanol discrimination, and this suggests that endogenously produced acetaldehyde does not contribute to the discriminative stimulus effects of ethanol. Together these results suggest that acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0 g/kg ethanol. [less ▲]

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See detailAcamprosate reduces context-dependent ethanol effects
Quertemont, Etienne ULg; Brabant, Christian ULg; De Witte, Philippe

in Psychopharmacology (2002), 164(1), 10-18

Rationale: Previous studies have indicated that the conditioned effects of environmental stimuli contribute to ethanol tolerance and abuse. Acamprosate was recently suggested to reduce the effects of ... [more ▼]

Rationale: Previous studies have indicated that the conditioned effects of environmental stimuli contribute to ethanol tolerance and abuse. Acamprosate was recently suggested to reduce the effects of environmental stimuli previously associated with ethanol administrations. This action is believed to contribute to the clinical benefits of acamprosate treatment in alcoholics. Objectives: In the present experiment, a classical drug-conditioning paradigm was used to test whether acamprosate modulates the effects of ethanol-paired environmental stimuli on spontaneous motor activity. Methods: Wistar rats were divided into three groups: cued, uncued and control. The cued group daily received ethanol injections (2.0 g/kg, IP) in a specific testing environment. The uncued group daily received ethanol injections (2.0 g/kg, IP) in their home cage but never experienced ethanol in the testing environment. The control group was injected with saline and never experienced ethanol. After 8 conditioning days, the rats were IP injected with various ethanol doses (saline, 1.0, 1.5 or 2.0 g/kg) and their spontaneous motor activity in the testing environment was recorded to investigate their respective tolerance to ethanol inhibitory effects. In the second part of the study, the same procedure was repeated with chronically acamprosate-treated rats. The chronic acamprosate treatment (400 mg/kg per day) started 2 weeks before the conditioning procedure by diluting acamprosate in the drinking bottles and was maintained throughout the whole experiment. Results: The cued rats showed a significant environment-dependent tolerance to ethanol inhibitory effects relative to the uncued and control rats. This higher ethanol tolerance of the cued rats was mainly due to a faster recovery from ethanol's inhibitory effects on spontaneous activity. Furthermore, the cued rats showed a higher level of activity in the testing environment after the saline injection. However, it is not clear whether this hyperactivity is a conditioned compensatory response or an increased exploratory behavior. Acamprosate totally abolished the environment-dependent tolerance to ethanol, whereas it did not alter the hyperactivity of the cued rats in the testing environment. Conclusions: The results of the present study suggest that acamprosate reduces ethanol-conditioned effects. Such an action may be of importance to explain the anti-relapse effects of acamprosate. [less ▲]

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See detailEffet placebo, effet nocebo: comment la science explique les guérions miraculeuses
Quertemont, Etienne ULg

Scientific conference (2002)

L’effet placebo est habituellement considéré comme l’ensemble des réponses psychologiques et physiologiques des patients à une substance inerte. On parle d’effet placebo lorsque cette réponse constitue un ... [more ▼]

L’effet placebo est habituellement considéré comme l’ensemble des réponses psychologiques et physiologiques des patients à une substance inerte. On parle d’effet placebo lorsque cette réponse constitue un effet bénéfique pour la santé et d’effet nocebo lorsque les conséquences sont néfastes. Cependant, les phénomènes placebo/nocebo recouvrent plus largement tous les effets du contexte environnemental qui ne résultent pas spécifiquement du traitement médical administré. Une partie de ce qu’on nomme effet placebo/nocebo peut s’expliquer par des mécanismes de conditionnement pavlovien. Des effets placebo résultant du conditionnement pavlovien sont ainsi régulièrement mis en évidence sur des animaux de laboratoire. Au conditionnement pavlovien s’ajoute également chez l’être humain un facteur plus spécifiquement psychologique : l’effet des croyances et des attentes (expectancies). De nombreuses études ont ainsi démontré que les croyances et les attentes des patients exercent des effets objectifs sur leur santé qui se traduisent par des modifications biologiques. Nous examinerons plus particulièrement les mécanismes qui permettent à ces influences psychologiques de modifier l’état biologique d’un sujet. Parmi ceux-ci, le système immunitaire ainsi que les opiacés endogènes qui régulent la douleur semblent particulièrement influencés par l’état psychologique. Finalement nous montrerons comment les phénomènes placebo/nocebo apportent une explication rationnelle à plusieurs exemples de guérisons miraculeuses ou pseudo-scientifiques. Parmi ces exemples nous examinerons plus particulièrement le rôle important que joue l’effet placebo dans l’homéopathie. [less ▲]

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See detailEthanol-conditioned withdrawal syndrome
Quertemont, Etienne ULg; De Witte, Philippe

in Proceedings of the 22nd European Winterconference on Brain Research (2002)

The withdrawal syndrome is closely related to the concepts of tolerance and physical dependence. The chronic consumption of a drug is believed to induce adaptive changes that are designed to oppose the ... [more ▼]

The withdrawal syndrome is closely related to the concepts of tolerance and physical dependence. The chronic consumption of a drug is believed to induce adaptive changes that are designed to oppose the acute effects of the drug. Such adaptive changes increase the tolerance to acute drug effects but lead to physical dependence, which is revealed by withdrawal symptoms when the drug is cleared from the body. However, another form of adaptive response to repeated drug consumption has been identified. This adaptive response appears after the intermittent repeated administration of a drug in association with the same set of environmental stimuli. After several associations, these environmental stimuli become able to induce a conditioned adaptive response. Such response leads to the phenomenon of “environment-dependent tolerance” that was observed with many drugs of abuse. However, if the drug is not administered, the conditioned stimuli alone may induce a “conditioned withdrawal syndrome”. Although less studied than the classical withdrawal syndrome, this conditioned withdrawal syndrome may be of importance for the development of drug dependence. In our experiments, we have studied the development of a conditioned withdrawal syndrome after repeated associations of a specific set of environmental stimuli with ethanol injections in Wistar rats. After repeated administrations of ethanol, the rats showed a clear environmental-dependent tolerance to ethanol. Furthermore, these conditioned stimuli induced behavioral (hyperexcitation) and neurochemical (increase glutamate release) responses similar to those observed after chronic alcohol withdrawal. [less ▲]

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See detailTime-course of brain ethanol levels and the acoustic startle response in the rat following the acute administration of ethanol
Williams, S. A.; Quertemont, Etienne ULg; Green, Heather et al

in Alcoholism, Clinical & Experimental Research (2001), 25

It is known that ethanol administration inhibits the acoustic startle response, but whether this sensitivity varies within-session has not been investigated. The purpose of the present study was to ... [more ▼]

It is known that ethanol administration inhibits the acoustic startle response, but whether this sensitivity varies within-session has not been investigated. The purpose of the present study was to compare the time-course of ethanol levels in brain with alterations in the acoustic startle response. Three experiments were conducted in adult male Sprague-Dawley rats. 1) Ethanol concentrations in brain were determined by microdialysis following the acute administration of 0.3, 1.0 and 3.0 g/kg ig of ethanol. 2) The effect of ethanol on the acoustic startle response was determined after the same doses. 3) The acoustic startle response was determined during two time periods, at 2-18 and 30-46 minutes, after ethanol administration to evaluate periods of ascending and descending ethanol levels. In expt. 1, brain levels of ethanol rose rapidly, peaking within 4-8 minutes following all doses. In expt. 2, ethanol administration reduced the acoustic startle response in a dose-related manner; all doses significantly reduced the response. In expt. 3, prepulse inhibition was diminished by ethanol during a very short period immediately after ethanol administration, whereas the acoustic startle response was inhibited only during later times. These data indicate that the acoustic startle response was exquisitely sensitive to ethanol, even at doses as low as 0.3 g/kg. In addition, prepulse inhibition was selectively disrupted immediately after ethanol administration, which suggests that this phenomenon may accompany the short-lived ascending limb of the brain ethanol curve. Supported by AA 12356 (DL) and AA11997. [less ▲]

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See detailConditioned stimulus preference after acetaldehyde but not ethanol injections
Quertemont, Etienne ULg; De Witte, Philippe

in Pharmacology, Biochemistry & Behavior (2001), 68

Acetaldehyde, the first ethanol metabolite, has been suggested to mediate some of the behavioral effects of ethanol and particularly its reinforcing properties, although this later hypothesis remains ... [more ▼]

Acetaldehyde, the first ethanol metabolite, has been suggested to mediate some of the behavioral effects of ethanol and particularly its reinforcing properties, although this later hypothesis remains extremely controversial. While several studies demonstrated the reinforcing effects of brain acetaldehyde, blood acetaldehyde accumulation is believed to be primarily aversive. In the present study, a conditioned reinforcement procedure has been used to investigate the reinforcing and/or aversive effects of intraperitoneal injections of both acetaldehyde and ethanol in Wistar rats. An olfactory stimulus was paired with daily injections of either ethanol (0, 0.25, 0.5, 1 and 2 g/kg) or acetaldehyde (0, 10, 20, 100 and 150 mg/kg). After eight conditioning sessions, all rats were tested for their stimulus preference or aversion. The results show that conditioning with small, 0.25 and 0.5 g/kg, ethanol doses induced neither preference nor aversion for the olfactory cue. In contrast, higher ethanol doses (1.0 and 2.0 g/kg) resulted in significant stimulus aversions. Acetaldehyde conditioning led to a biphasic stimulus preference, with a maximal preference around 20 mg/kg acetaldehyde. No evidence of aversive effects was found with increasing doses of acetaldehyde, even with concentrations close to the lethal limit. The present study clearly shows that systemic acetaldehyde injections induced significant stimulus preferences. This suggests that acetaldehyde may be, at least in part, responsible for the reinforcing effects of alcohol intake. [less ▲]

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See detailEthanol-induced taurine release in rats genetically selected for ethanol preference and sensitivity
Quertemont, Etienne ULg; Colombo, Giancarlo; De Witte, Philippe

in Alcohol & Alcoholism (2001), 36

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See detailImplications of acetaldehyde in ethanol reinforcing and discriminative effects
Quertemont, Etienne ULg; Rios, Ananda; Macias, Enrique et al

in Alcohol & Alcoholism (2001), 36

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See detailEthanol-induced brain extracellular taurine release: an osmoregulatory mechanism?
Quertemont, Etienne ULg; Devitgh, Audrey; De witte, Philippe

in Alcohol & Alcoholism (2001), 36

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See detailNeurochemical and behavioral effects of ethnaol-conditioned stimuli: implication for alcohol consumption
Quertemont, Etienne ULg; De Witte, Philippe

in Cahiers de l'I.R.E.B. (2001), 15

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See detailEffets comportementaux et neurochimiques de stimuli associés à l’administration d'éthanol: implications pour les comportements d'alcoolisation
Quertemont, Etienne ULg; De Witte, Philippe

in Cahiers de l'I.R.E.B. (2001), 15

Les drogues, y compris l’alcool, peuvent servir de stimuli inconditionnels dans des situations d’apprentissage par conditionnement. Les stimuli environnementaux qui accompagnent systématiquement ... [more ▼]

Les drogues, y compris l’alcool, peuvent servir de stimuli inconditionnels dans des situations d’apprentissage par conditionnement. Les stimuli environnementaux qui accompagnent systématiquement l’administration d’alcool peuvent ainsi acquérir le statut de stimuli conditionnés capables d’induire à eux seuls des réactions physiologiques conditionnées. Deux types de réactions conditionnées avec l’alcool ont été observées. D’une part, les stimuli associés à l’administration d’alcool peuvent induire des effets similaires à ceux de l’éthanol. D’autre part, ces stimuli conditionnés à l’éthanol peuvent aussi engendrer des réponses conditionnées opposées aux effets de l’éthanol. Ces deux types de réponses conditionnées semblent jouer un rôle dans les différentes étapes de l’alcoolisation. Leur implication dans la tolérance envers l’éthanol est largement illustrée par le phénomène de tolérance dépendante de l’environnement. Plusieurs études expérimentales et observations cliniques suggèrent aussi que les processus de conditionnement pourraient être impliqués dans la consommation d’alcool et particulièrement dans son abus. Toutefois, les bases neurochimiques de ces réponses conditionnées à l’éthanol sont encore largement méconnues. De récentes études utilisant la technique de microdialyse intracérébrale ont pourtant montré le rôle de divers neurotransmetteurs et neuromodulateurs. D’une part, les réponses conditionnées similaires à l’éthanol sont accompagnées d’une libération de dopamine dans le noyau accumbens. D’autre part, la libération conditionnée de glutamate et de taurine semble être impliquée dans les réponses conditionnées opposées aux effets de l’éthanol. [less ▲]

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See detailTaurine and ethanol preference : a microdialysis study using Sardinian alcohol-preferring and non-preferring rats
Quertemont, Etienne ULg; Lallemand, Frédéric; Colombo, Giancarlo et al

in European Neuropsychopharmacology (2000), 10

Recent intracerebral microdialysis studies of different rat brain regions have shown that an acute ethanol injection induced a rapid dose-dependent increase in taurine microdialysate content during the ... [more ▼]

Recent intracerebral microdialysis studies of different rat brain regions have shown that an acute ethanol injection induced a rapid dose-dependent increase in taurine microdialysate content during the first 60-min period. In taurine-supplemented rats, a reduced aversion for high ethanol doses was observed in a place conditioning paradigm, suggesting that taurine may be implicated in the regulation of some adverse effects of ethanol. The present study compares the effects of acute ethanol injections (1.0 and 2.0 g/ kg, i.p.) on taurine nucleus accumbens microdialysate content in Sardinian ethanol-preferring (sP) and Sardinian ethanol-non preferring (sNP) rats. While neither saline nor 1.0 g/kg ethanol injections had significant effect on taurine microdialysate concentration, 2.0 g/kg ethanol administration induced a rapid and significant increase in taurine microdialysate content in both sP and sNP rats. However, this ethanol-induced taurine release was significantly reduced in sP rats by comparison to sNP rats. As taurine is suggested to be released by brain cells to modulate different ethanol adverse effects, this lower taurine responsiveness to ethanol in sP rats by comparison to both sNP and Wistar rats may be a relevant indicator of reduced ethanol aversive effects in such animals and therefore be related to their higher alcohol consumption. [less ▲]

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See detailBehavioral and neurochemical effects induced by alcohol-conditioned stimuli
Quertemont, Etienne ULg; De Witte, Philippe

in Cahiers de l'I.R.E.B. (2000), 14

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See detailEthanol induces taurine release in the amygdala: an in vivo microdialysis study
Quertemont, Etienne ULg; Dahchour, Abdelkhader; Ward, Roberta J. et al

in Addiction Biology (1999), 4

The effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with the total ... [more ▼]

The effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with the total brain ethanol content. Each acute intraperitoneal injection of ethanol, 0.5, 1.0, 2.0 and 3.0 g/kg body weight, induced an immediate increase in the microdialysate taurine content; both 0.5 and 1.0 g/kg ethanol evoked an increase during the first 20 minutes following injection which returned to baseline value by 40 minutes despite the fact that ethanol was detectable in the brain until 60 or 120 minutes respectively; after either 2.0 or 3.0 g/kg ethanol there was an increase in taurine content of gradual intensity which gradually declined to reach baseline values by 100 minutes. In contrast, the ethanol concentration for 2.0 g/kg remained elevated at the end of the 120 minutes approximately 25 mg ethanol / mg protein. The stimulated release of taurine within the amygdala could participate in the regulation of the ethanol-induced changes in osmolarity, since taurine is postulated to act as an osmoregulator in the brain. Taurine could also mediate or interact with the ethanol-induced CNS effects, as it exerts a modulatory action on cell excitability and neurotransmitter processes. [less ▲]

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See detailBases neurobiologiques des comportements d’alcoolisation: implication des acides aminés neuro-excitateurs et neuro-inhibiteurs
Quertemont, Etienne ULg

Doctoral thesis (1999)

Les théories traditionnelles qui essaient d’expliquer le phénomène d’addiction rencontrent généralement de grandes difficultés à rendre compte de deux particularités importantes de cet état de ... [more ▼]

Les théories traditionnelles qui essaient d’expliquer le phénomène d’addiction rencontrent généralement de grandes difficultés à rendre compte de deux particularités importantes de cet état de pharmacodépendance: le caractère compulsif de la consommation de drogue et la très grande fréquence des rechutes parfois très longtemps après le sevrage. Les théories de l’apprentissage par conditionnement apportent une solution originale à ces questions non résolues. En effet, de nombreuses expériences animales ont démontré que des stimuli environnementaux associés de manière répétée à l’administration de ces drogues peuvent acquérir le statut de stimuli conditionnés capables d’induire à eux seuls certains effets physiologiques et comportementaux spécifiques. On a de plus suggéré que ces réponses conditionnées sont responsables du déclenchement des comportements compulsifs de recherche de drogue et participent dès lors aux rechutes dans sa consommation incontrôlée. Parmi les drogues addictives, l’alcool est probablement la substance la plus difficile à étudier. En effet, sa simplicité moléculaire lui permet paradoxalement d’affecter tous les systèmes de neurotransmission cérébrale. Il est donc difficile d’identifier clairement les bases neurochimiques des différents effets psychotropes de l’alcool. D’autre part, la littérature scientifique confirme également le rôle des apprentissages par conditionnement dans le maintien de la consommation d’alcool et dans l’alcoolodépendance. Bien que l’importance des réponses conditionnées à l’éthanol est maintenant reconnue, les bases neurochimiques de ces effets conditionnés sont encore méconnues. Le présent travail est donc destiné à faire le point sur les connaissances actuelles des bases neurochimiques et comportementales de la consommation d’alcool et de l’addiction alcoolique. Plus particulièrement les neurotransmetteurs acides aminés ont fait l’objet d’investigations expérimentales destinées à élucider leur rôle dans les effets conditionnés à l’éthanol. [less ▲]

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See detailEthanol neurotoxicity: from basic science to clinical reality
De Witte, Philippe; Ward, Roberta; Dahchour, Abdelkhader et al

in Alcohol & Alcoholism (1999), 34

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See detailChanges in the amygdala amino acid microdialysate after conditioning with a cue associated with ethanol
Quertemont, Etienne ULg; de Neuville, Jessica; De Witte, Philippe

in Alcohol & Alcoholism (1999), 34

The excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values such that it may play a key role in ... [more ▼]

The excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values such that it may play a key role in conditioned drug effects. In the present studies, the responses of the excitatory amino acids, aspartate and glutamate together with the neuromodulatory sulphonated amino acid taurine, within the basolateral amygdala, to an odor cue repeatedly associated with acute ethanol injections (2g/kg, IP) have been investigated by a microdialysis technique combined with HPLC-EC analysis. After presentation of the ethanol-conditioned stimulus, a single IP saline injection induced an immediate and significant increase in the taurine microdialysate content which could be related to the neuromodulatory action of taurine. Furthermore, when the conditioned stimulus was combined with the ethanol injection (2g/kg, IP), significant increases in both taurine and glutamate microdialysate content were observed and indicated a learned compensatory response to counteract the acute effects of ethanol. These results demonstrate that changes in amygdala extracellular glutamate and taurine concentrations can be conditioned to ethanol-associated stimuli and are therefore probably implicated in the phenomenon of environmental-dependent tolerance to ethanol. [less ▲]

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See detailAlcohol-non-preferring Sardinian rats exhibit a higher ethanol-induced taurine increase compared to alcohol-preferring Sardinian rats: a microdialysis study
Quertemont, Etienne ULg; Lallemand, Frédéric; Colombo, Giancarlo et al

in Alcohol & Alcoholism (1999), 34

It is well known that ethanol injections induce increases in the extracellular taurine concentration from various rat brain regions. Furthermore, recent studies have shown that taurine supplementation ... [more ▼]

It is well known that ethanol injections induce increases in the extracellular taurine concentration from various rat brain regions. Furthermore, recent studies have shown that taurine supplementation modulates the ethanol reinforcing effects in a place conditioning experiment. However, it is unknown whether there is a relationship between this taurine increase and the ethanol drinking behaviors. In the present microdialysis experiments, we compared the effects of ethanol injections (1.0 and 2.0 g/kg) on the extracellular taurine concentration from the nucleus accumbens of either Sardinian alcohol-preferring or Sardinian alcohol-non-preferring rats which have been selectively bred for their differential ethanol preference. The results show that acute ethanol produces an immediate increase in the taurine microdialysate content from both rat lines. However, this increase in taurine microdialysate content was more potent in the alcohol-non-preferring rats. Since taurine has been postulated to be released by brain cells to modulate some of the adverse effects of ethanol, the higher increase in taurine microdialysate content in the alcohol-non-preferring rats is probably related to their higher vulnerability to ethanol aversive effects. [less ▲]

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See detailChanges in the amygdala amino acid microdialysate after conditioning with a cue associated with ethanol
Quertemont, Etienne ULg; De Neuville, Jessica; De Witte, Philippe

in Psychopharmacology (1998), 139

Excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values, such that it may play a key role in ... [more ▼]

Excitatory amino acid neurotransmission within the amygdala has been implicated in learning associations between external stimuli and intrinsic reward values, such that it may play a key role in conditioned drug effects. In the present studies, the responses of the excitatory amino acids, aspartate and glutamate, together with the neuromodulatory sulphonated amino acid, taurine, within the basolateral amygdala, to an odor cue repeatedly associated with acute ethanol injections (2 g/kg, IP) have been investigated by a microdialysis technique combined with HPLC-EC analysis. After presentation of the ethanol-conditioned stimulus, a single IP saline injection induced an immediate and significant increase in the taurine microdialysate content which could be related to the neuromodulatory action of taurine. Furthermore, when the conditioned stimulus was combined with the ethanol injection (2 g/kg, IP), significant increases in both taurine and glutamate microdialysate content were observed and indicated a learned compensatory response to counteract the acute effects of ethanol. These results demonstrate that changes in amygdala extracellular glutamate and taurine concentrations can be conditioned to ethanol-associated stimuli and are therefore probably implicated in the phenomenon of environmental-dependent tolerance to ethanol. [less ▲]

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