References of "Tirelli, Ezio"
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See detailMale aromatase knockout mice acquire a conditioned place preference for cocaine but not for contact with an estrous female
Pierman, S.; Tirelli, Ezio ULiege; Douhard, Quentin ULiege et al

in Behavioural Brain Research (2006), 174(1), 64-69

We have previously shown that male mice carrying a targeted mutation in the Cyp19 gene which encodes the aromatase enzyme (aromatase knockout or ArKO), showed a reduced interest to investigate volatile ... [more ▼]

We have previously shown that male mice carrying a targeted mutation in the Cyp19 gene which encodes the aromatase enzyme (aromatase knockout or ArKO), showed a reduced interest to investigate volatile odors from conspecifics in a Y-maze. We asked here whether the incentive value of reproductively relevant odors is reduced in ArKO males by comparing the ability of male wild-type (WT) and ArKO mice to learn a conditioned place preference using exposure to reproductively relevant odors as incentive stimuli. When the presence of an anesthetized estrous female or soiled bedding from estrous females was used as incentive stimuli, only WT and not male ArKO mice showed conditioned place preference suggesting that the reward value of these stimuli is reduced in ArKO males. However, ArKO males showed conditioned place preference when cocaine was used as incentive stimulus, indicating that ArKO males are able to learn the conditioned place preference procedure. These results thus further confirm the important role of estradiol in sexually related behavioral responses in male mice. [less ▲]

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See detailMice lacking the melanin-concentrating hormone receptor-1 exhibit an atypical psychomotor susceptibility to cocaine and no conditioned cocaine response
Tyhon, Amélie ULiege; Adamantidis, Antoine ULiege; Foidart, Agnès ULiege et al

in Behavioural Brain Research (2006), 173(1), 94-103

The present study aimed at characterizing the acute and intermittent psychomotor responsiveness to cocaine in mice lacking the MCHR1 receptor, which is thought to modulate the mesocorticolimbic sytem ... [more ▼]

The present study aimed at characterizing the acute and intermittent psychomotor responsiveness to cocaine in mice lacking the MCHR1 receptor, which is thought to modulate the mesocorticolimbic sytem functioning [Smith DG, Tzavara ET, Shaw J, Luecke S, Wade M, Davis R, et al. Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor deficient mice. J Neurosci 2005;25:914-22]. On a first free-drug session, MCHR1-deficient mice exhibited significantly higher levels of locomotor activity elicited by the novelty of the test chambers than their wild-type counterparts. On the following day session, a first injection of 6 or 12mg/kg cocaine induced comparable dose-related psychomotor activations in both genotypes, without significant difference in the relative increase in locomotion. Over the following eight once-daily test sessions, the slight psychomotor increase induced by 6mg/kg was equivalent in both genotypes and constant over the sessions. At 12mg/kg, cocaine induced a clear-cut incremental responsiveness to cocaine in both genotypes on the three first sessions; on the following sessions, only the wild-types displayed an incremental responsiveness until the last session, a sensitized effect that was confirmed for the wild-types but not for the knockouts on a subsequent sensitization test (cocaine challenge). Finally, the knockouts did not exhibit any sign of cocaine-conditioning (saline challenge), contrarily to the wild-types. It is speculated that MCHR1 may contribute to the neurobiological mechanisms of conditioned cocaine-induced psychomotor effects, possibly to those underpinning sensitization, and to a lesser extent to those sub-serving acute pharmacological cocaine action. [less ▲]

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See detailEffects of the H-3-receptor inverse agonist thioperamide on the psychornotor effects induced by acutely and repeatedly given cocaine in C57BL/6J mice
Brabant, Christian ULiege; Quertemont, Etienne ULiege; Tirelli, Ezio ULiege

in Pharmacology, Biochemistry & Behavior (2006), 83(4), 561-569

Previous studies have shown that histamine H(3) blockers potentiate the psychomotor and rewarding effects of cocaine. The present study examined the influence of thioperamide, an inverse H(3) receptor ... [more ▼]

Previous studies have shown that histamine H(3) blockers potentiate the psychomotor and rewarding effects of cocaine. The present study examined the influence of thioperamide, an inverse H(3) receptor agonist, on the development of psychomotor sensitization and stereotyped activity induced by acute or intermittent cocaine in C57BL/6J mice. In the first experiment, mice were injected i.p. with saline, 10 or 20mg/kg thioperamide and saline or 8mg/kg cocaine, 10min apart, before being tested for their locomotor activity (providing data on the acute effects of thioperamide on cocaine-induced activity). Subsequently, mice were treated in the same manner every other day over six additional sessions. Sensitization was assessed by the responsiveness to a cocaine challenge (8mg/kg, i.p.) given 2 and 14days following the intermittent treatment. In experiments 2 and 3, we tested the effects of thioperamide (10 or 20mg/kg, i.p.) on gnawing and sniffing induced or affected by relatively high doses of cocaine (24 or 32mg/kg, s.c.), the drugs being given 10min apart. In the first experiment, both doses of thioperamide amplified cocaine-induced psychomotor hyperactivity almost on all experimental sessions. However, the histamine inverse agonist did not affect the induction of a psychomotor sensitization. All cocaine-treated mice showed similar levels of sensitized activity 2 and 14days after the intermittent treatments, whether they received thioperamide or not. The second and the third experiments showed that thioperamide did not affect gnawing and sniffing induced by cocaine. Taken together, these results indicate that H(3) receptors clearly contribute to the neurobiological mechanisms of the locomotor component of cocaine-induced psychomotor activation, but less likely to those underlying the development of cocaine behavioral sensitization or the expression of cocaine-induced oro-facial stereotypies. [less ▲]

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See detailLocomotor effects of ethanol and acetaldehyde after peripheral and intraventricular injections in Swiss and C57BL/6J mice
Tambour, Sophie ULiege; Didone, Vincent ULiege; Tirelli, Ezio ULiege et al

in Behavioural Brain Research (2006), 172(1), 145-154

Several studies have suggested that acetaldehyde, the first product of ethanol metabolism, is involved in the locomotor stimulant effects of ethanol in mice, although it has never been formally tested ... [more ▼]

Several studies have suggested that acetaldehyde, the first product of ethanol metabolism, is involved in the locomotor stimulant effects of ethanol in mice, although it has never been formally tested whether acetaldehyde injected directly into the brain of mice has stimulant properties. Recently, it was also shown in rats that both ethanol and acetaldehyde can induce opposite locomotor effects according to the route of administration. Whereas peripheral administrations of ethanol and acetaldehyde induced locomotor depressant effects, their infusions directly into the brain produced locomotor stimulation. The aim of the present study was to characterize in mice the locomotor effects of ethanol and acetaldehyde injected either peripherally by the intraperitoneal route or centrally into the brain ventricles. Additionally, the effects of ethanol and acetaldehyde were compared in two strains of mice known for their differential sensitivity to the locomotor effects of ethanol, namely Swiss and C57BL/6J mice. Ethanol induced a biphasic effect on locomotor activity in Swiss mice, with stimulant effects at low to moderate doses and depressant effects at higher doses. Such a profile of effects was observed whatever the route of administration, peripheral or central. In C57BL/6J mice, ethanol only induced monophasic depressant effects. In this mouse strain, no evidence of the stimulant effects of ethanol was found after either an i.p. or an i.c.v. administration of ethanol. In contrast to ethanol, acetaldehyde yielded only depressant effects in both strains of mice after both peripheral and central administrations. These results indicate that the route of administration does not alter the locomotor effects of ethanol and acetaldehyde in mice. Additionally, the present study shows that the stimulant properties of acetaldehyde, even after direct infusion into the brain, are not as obvious as previously speculated. [less ▲]

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See detailCocaine-conditioned activity persists for a longer time than cocaine-sensitized activity in mice: Implications for the theories using Pavlovian excitatory conditioning to explain the context-specificity of sensitization
Tirelli, Ezio ULiege; Michel, Alexa ULiege; Brabant, Christian ULiege

in Behavioural Brain Research (2005), 165(1), 18-25

The present study was aimed at testing the prediction of the Pavlovian excitatory conditioning explanation of context-specific sensitization that the sensitized effect (SE) should persist as long as the ... [more ▼]

The present study was aimed at testing the prediction of the Pavlovian excitatory conditioning explanation of context-specific sensitization that the sensitized effect (SE) should persist as long as the post-sensitization conditioned activity (CR). C57BL/6J mice were tested for the expression of cocaine-induced conditioned and sensitized locomotion on several intervals after the establishment of a sensitization in an unchanging context. A group of mice received 10 once-daily injections of 10 mg/kg cocaine (s.c.) in a short time prior to being tested in activity-meters for 60 min sessions (cocaine-pretreated group), mice from a control group receiving saline in the same manner (saline-pretreated group). On the test sessions, taking place 1, 8 and 28 days after cocaine pretreatment, half of the animals of each pretreatment group (n=8) received a challenge test with saline and the other half with 10 mg/kg cocaine in the pretreatment context room (for CR and SE tests, respectively). The CR was significantly expressed on the three successive saline-challenge tests, albeit the activity levels were markedly decreased on the 28-day retention test. In contrast, the SE was significantly expressed only during the first half of the 1-day test session and the first 10 min of the 8-day test session, no SE effect being expressed on the 28-day retention test. The results, suggesting a functional uncoupling of the CR from the SE, disprove the theories of context-specificity of sensitization based completely or partially on Pavlovian excitatory conditioning mechanisms. [less ▲]

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See detailDisrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive and NMDA response deficit
Grisar, Thierry ULiege; Adamantidis, Antoine ULiege; Thomas, Elizabeth et al

in Journal of the Neurological Sciences (2005, November 15), 238(Suppl. 1), 288

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See detailDisrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function.
Adamantidis, Antoine ULiege; Thomas, Elizabeth; Foidart, Agnès ULiege et al

in European Journal of Neuroscience (2005), 21(10), 2837-44

In order to investigate the physiological properties of the melanin-concentrating hormone (MCH) we have generated and used mice from which the MCH receptor 1 gene was deleted (MCHR1(Neo/Neo) mice ... [more ▼]

In order to investigate the physiological properties of the melanin-concentrating hormone (MCH) we have generated and used mice from which the MCH receptor 1 gene was deleted (MCHR1(Neo/Neo) mice). Complementary experimental approaches were used to investigate alterations in the learning and memory processes of our transgenic model. The ability of the knockout strain to carry out the inhibitory passive avoidance test was found to be considerably impaired although no significant differences were observed in anxiety levels. This impaired cognitive property prompted us to explore modifications in N-methyl D-aspartate (NMDA) responses in the hippocampus. Intracellular recordings of CA1 pyramidal neurons in hippocampal slices from the MCHR1(Neo/Neo) mice revealed significantly decreased NMDA responses. Finally, using in situ hybridization we found a 15% reduction in NMDAR1 subunit in the CA1 region. These results show for the first time a possible role for MCH in the control of the function of the NMDA receptor. [less ▲]

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See detailThe role of acetaldehyde in the neurobehavioral effects of ethanol : a comprehensive review of animal studies
Quertemont, Etienne ULiege; Tambour, Sophie ULiege; Tirelli, Ezio ULiege

in Progress in Neurobiology (2005), 75(4), 247-274

Acetaldehyde has long been suggested to be involved in a number of ethanol's pharmacological and behavioral effects, such as its reinforcing, aversive, sedative, amnesic and stimulant properties. However ... [more ▼]

Acetaldehyde has long been suggested to be involved in a number of ethanol's pharmacological and behavioral effects, such as its reinforcing, aversive, sedative, amnesic and stimulant properties. However, the role of acetaldehyde in ethanol's effects has been an extremely controversial topic during the past two decades. Opinions ranged from those virtually denying any role for acetaldehyde in ethanol's effects to those who claimed that alcoholism is in fact "acetaldehydism". Considering the possible key role of acetaldehyde in alcohol addiction, it is critical to clarify the respective functions of acetaldehyde and ethanol molecules in the pharmacological and behavioral effects of alcohol consumption. In the present paper, we review the animal studies reporting evidence that acetaldehyde is involved in the pharmacological and behavioral effects of ethanol. A number of studies demonstrated that acetaldehyde administration induces a range of behavioral effects. Other pharmacological studies indicated that acetaldehyde might be critically involved in several effects of ethanol consumption, including its reinforcing consequences. However, conflicting evidence has also been published. Furthermore, it remains to be shown whether pharmacologically relevant concentrations of acetaldehyde are achieved in the brain after alcohol consumption in order to induce significant effects. Finally, we review current evidence about the central mechanisms of action of acetaldehyde. (c) 2005 Elsevier Ltd. All rights reserved. [less ▲]

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See detailThe H(3) antagonist thioperamide reveals conditioned preference for a context associated with an inactive small dose of cocaine in C57BL/6J mice
Brabant, Christian ULiege; Charlier, Yana ULiege; Quertemont, Etienne ULiege et al

in Behavioural Brain Research (2005), 160(1), 161-168

The histaminergic system has been speculated to be involved in the inhibitory control of drug reward, H-1 and H-2 antagonists having been found to potentiate conditioned place preference induced by ... [more ▼]

The histaminergic system has been speculated to be involved in the inhibitory control of drug reward, H-1 and H-2 antagonists having been found to potentiate conditioned place preference induced by morphine or cocaine. In contrast, the role of H-3 receptors in cocaine-induced place preference is still unknown. The present study tested the effects of thioperamide (0, 10 and 20 mg/kg, i.p.), an H-3 autoreceptor antagonist, on the development of a conditioned place preference induced by cocaine (0, 2 and 8 mg/kg, i.p.) in C57BL/6J mice. Thioperamide was injected 10 min before each cocaine-pairing session. The activity scores recorded on the first cocaine-pairing session were also used to test the effects of thioperamide on cocaine-induced locomotor activity. Thioperamide alone had no reinforcing effects and did not affect the conditioned place preference induced by 8 mg/kg cocaine. However, thioperamide dose-dependently revealed a conditioned place preference induced by 2 mg/kg cocaine, a dose that was inactive per se. Finally, thioperamide dose-dependently potentiated the stimulant effects of cocaine, in spite of its slight hypolocomotor effect when given alone. Our results strongly suggest that H3 antagonists potentiate the stimulant and reinforcing effects of cocaine in mice. © 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailInfluence of the dose and the number of drug-context pairings on the magnitude and the long-lasting retention of cocaine-induced conditioned place preference in C57BL/6J mice
Brabant, Christian ULiege; Quertemont, Etienne ULiege; Tirelli, Ezio ULiege

in Psychopharmacology (2005), 180(1), 33-40

Rationale: The place conditioning procedure is increasingly used to study relapse in drug seeking in mice. However, the retention course of drug-induced place preference has not been systematically ... [more ▼]

Rationale: The place conditioning procedure is increasingly used to study relapse in drug seeking in mice. However, the retention course of drug-induced place preference has not been systematically characterized. Methods: The effects of cocaine doses and number of conditioning trials on both the magnitude and the persistence of cocaine-induced conditioned place preference (CPP) were investigated in C57BL/6J mice. Twelve groups of animals were injected with saline, 4, 8 or 12 mg/kg cocaine (i.p.) and submitted to an unbiased counterbalanced place conditioning protocol including one, two or four drug-pairing sessions. Subsequently, the animals were tested at various time intervals after the last conditioning session. Results: One cocaine-pairing session was insufficient to induce a CPP. Two and four pairing sessions resulted in significant place preferences of similar magnitude for all tested doses of cocaine, the place preference induced by the greatest number of pairing sessions being the strongest. In the two-pairing groups, place preference lasted less than 14 days for any tested dose of cocaine. In contrast, all four-pairing groups still showed significant place preference 28 days after the last conditioning session. However, the magnitude of cocaine place preference slowly declined at a rate that was dependent upon cocaine dose. On the 35-day post-conditioning interval, only the 12-mg/kg cocaine group still displayed a significant place preference, whereas place preference was undetectable at 42 and 56 days post-conditioning for all groups. Conclusions: The number of cocaine-pairing sessions, but not cocaine dose, affected the magnitude of cocaine place preference in mice when tested 1 day after the last conditioning session. In contrast, both cocaine doses and the number of pairing sessions affected the persistence of cocaine place preference. Overall, these results demonstrate that cocaine-induced place preference is a long lasting phenomenon that is strongly affected by the number of drug-pairing trials. [less ▲]

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See detailDissociation between the locomotor and anxiolytic effects of acetaldehyde in the elevated plus-maze : evidence that acetaldehyde is not involved in the anxiolytic effects of ethanol in mice
Tambour, Sophie ULiege; Didone, Vincent ULiege; Tirelli, Ezio ULiege et al

in European Neuropsychopharmacology (2005), 15(6), 655-662

Acetaldehyde, the first product of ethanol metabolism, has been suggested to play a major role in many behavioral effects of ethanol. However, very few studies have directly tested the behavioral effects ... [more ▼]

Acetaldehyde, the first product of ethanol metabolism, has been suggested to play a major role in many behavioral effects of ethanol. However, very few studies have directly tested the behavioral effects of the acute administration of acetaldehyde. In particular, the role of this metabolite in ethanol-induced anxiolytic effects has never been extensively tested. The aim of the present study was to characterize the anxiolytic effects of acetaldehyde in two strains of mice, C57BL/6J and CD1 mice with the elevated plus-maze procedure. The results show that acute injections of ethanol (1-2 g/kg) induced significant dose-dependent anxiolytic effects in both strains of mice. In contrast, acetaldehyde failed to produce any anxiolytic effect, although it induced a significant hypolocomotor effect at the highest doses. In an independent experiment, cyanamide, an aldehyde dehydrogenase inhibitor, prevented the locomotor stimulant effects of ethanol, although it failed to alter its anxiolytic effects. Together, the results of the present study indicate that acetaidehyde is not involved in ethanol-induced anxiolytic effects, although it may be involved in its sedative/hypolocomotor effects. (c) 2005 Elsevier BX and ECNP. All fights reserved. [less ▲]

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See detailEvidence that the relations between novelty-induced activity, locomotor stimulation and place preference induced by cocaine qualitatively depend upon the dose: A multiple regression analysis in inbred C57BL/6J mice
Brabant, Christian ULiege; Quertemont, Etienne ULiege; Tirelli, Ezio ULiege

in Behavioural Brain Research (2005), 158(2), 201-210

It has been speculated that an individual's response to novelty is a reliable predictor of its vulnerability to develop addiction. However, the relationships between response to novelty and the ... [more ▼]

It has been speculated that an individual's response to novelty is a reliable predictor of its vulnerability to develop addiction. However, the relationships between response to novelty and the development of drug-induced conditioned place preference are still unclear. The present study investigates the relationships between locomotor responses to novelty, cocaine-induced locomotor stimulation and conditioned place preference in C57BL/6J mice with multiple regression analyses. Four groups of mice receiving saline, 4, 8 or 12 mg/kg cocaine (i.p.) were submitted to an 8-day unbiased counterbalanced place conditioning protocol. Levels of locomotion on the pre-conditioning session were used as a score of locomotor response to a novel environment. The locomotor activity on the first cocaine-pairing session of the conditioning procedure served as a measure of the locomotion-activating response to a single injection of cocaine. Cocaine-induced dose-dependent locomotor stimulant effects and a significant place preference at all tested doses. A positive correlation was found between the locomotor responses to novelty and the locomotor stimulant effects of cocaine, but was significant only for the highest dose of cocaine (12 mg/kg). In contrast, there was a negative correlation between the locomotor response to novelty and the conditioned place preference induced by 4 mg/kg cocaine. Finally, the locomotor stimulant effects of cocaine do not correlate with cocaine-induced conditioned place preference at any tested dose of cocaine. The relationships between locomotor response to novelty and both cocaine-induced stimulant and rewarding effects can be differentially affected by the dose in inbred C57BL/6J mice. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailEffects of centrally versus peripherally administered ethanol in C57BL/6J and CD1 mice
Tambour, Sophie ULiege; Didone, Vincent ULiege; Quertemont, Etienne ULiege et al

in Behavioural Pharmacology (2005), 16

Locomotor activation is often reported to occur after a systemic administration of low doses of ethanol in most mouse strains, as for example outbred CD1 mice. However, in some strains of mice, such as ... [more ▼]

Locomotor activation is often reported to occur after a systemic administration of low doses of ethanol in most mouse strains, as for example outbred CD1 mice. However, in some strains of mice, such as the inbred C57BL/6J mice, and in rats, systemic injections of ethanol typically induce only a depression of the locomotor activity. Recently, Correa et al. (2003) showed that direct infusions of ethanol in the brain ventricles of rats induced locomotor stimulant effects. These authors suggested that some undefined peripheral effects of ethanol may mask its central stimulant effects when ethanol is administered intraperitoneally. The aim of the present study was to investigate the locomotor effects of either intraperitoneal and intracerebroventricular ethanol administrations in two strains of mice, outbred CD1 and inbred C57BL/6J, that are respectively characterized by the presence and absence of a locomotor stimulant response to ethanol. The results showed that ethanol at moderate and high doses induced locomotor depressant effects in C57BL/6J mice whatever the route of ethanol administration. In contrast, ethanol induced a biphasic effect on locomotor activity in CD1 mice with a stimulant response at low doses followed by a significant sedation. Such a response to ethanol was observed after both peripheral and central administrations of ethanol. The results of the present study demonstrate that the locomotor effects of ethanol in mice are not affected by the route of administration, i.e. peripheral or central. In these rodents, there is no evidence that unidentified peripheral effects of ethanol mask the stimulant ethanol effects. [less ▲]

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See detailModulatory function of the H3 histaminergic receptor system in addiction: an example with cocaine and ethanol
Brabant, Christian ULiege; Didone, Vincent ULiege; Tirelli, Ezio ULiege et al

Poster (2005)

The histaminergic neurotransmission is involved in many biological functions, including the modulation of arousal, fluid balance, food intake, reinforcement and learning. Recently, the results of several ... [more ▼]

The histaminergic neurotransmission is involved in many biological functions, including the modulation of arousal, fluid balance, food intake, reinforcement and learning. Recently, the results of several studies have also suggested that the central histaminergic system, and particularly the H3 receptors, plays a role in drug addiction. For example, in animal experiments, the administration of H3 agonists and antagonists modulate the self-administration of various drugs including cocaine, amphetamine and alcohol. In the present studies, we used the locomotor stimulant effects of drugs as an index of their abuse potential (most of addictive drugs stimulate locomotor activity, at least at some doses, and this effect is often considered as an intrinsic feature of drug addiction). In two independent experiments, we tested the effects of thioperamide, a histamine H3 antagonist/inverse agonist, on the locomotor stimulant effects of cocaine and ethanol. Our results show that thioperamide modulates the locomotor stimulant effects of both cocaine and ethanol. However, this modulatory effect was surprisingly opposite in direction depending upon the tested drug. Whereas thioperamide potentiated the locomotor stimulant effect of cocaine, it prevented the hyperactivity induced by 2 g/kg ethanol in mice. In the brain, H3 receptors is both a histamine autoreceptor modulating the synaptic release of histamine and a heteroreceptor that modulates the release of other neurotransmitters such as dopamine, acetylcholine and GABA. It is therefore likely that the modulatory action of thioperamide on cocaine and ethanol stimulant effects involves different neurotransmitter system. This conclusion is supported by our preliminary results on knock-out mice genetically devoid of histamine. In such knock-out mice, ethanol retains its stimulant properties, suggesting that histamine release is not involved in this effect. In contrast, these knock-out mice showed a reduced cocaine-induced hyperactivity, indicating that histamine release play a significant role in the stimulant effect of cocaine. [less ▲]

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See detailHistamine H3 antagonist thioperamide dose-dependently enhances memory consolidation and reverses amnesia induced by dizocilpine or scopolamine in a one-trial inhibitory avoidance task in mice
Bernaerts, P.; Lamberty, Y.; Tirelli, Ezio ULiege

in Behavioural Brain Research (2004), 154(1), 211-219

In the literature, there is some evidence indicating that H3 histamine receptor antagonists, in particular thioperamide, can facilitate learning and memory retrieval in laboratory rodents. The present ... [more ▼]

In the literature, there is some evidence indicating that H3 histamine receptor antagonists, in particular thioperamide, can facilitate learning and memory retrieval in laboratory rodents. The present study aimed at verifying whether this also holds for memory consolidation, a phase of memory for which there is scarcity of convincing data on the effects of H3 receptor antagonists given systemically. To that end, memory consolidation was assessed in C57BL/6J mice using the one-trial step-through inhibitory avoidance task, the compounds being injected immediately after training (foot-shock) and performance measured 24 h later. More specifically, the following effects of thioperamide (1.25-20 mg/kg) were dose-dependently analysed: (1) its potential direct effects on memory consolidation; (2) its potential reversing effects on retrograde amnesia induced by the NMDA antagonist dizocilpine (MK-801, 0.5 mg/kg) and (3) its potential reversing effects on the well-known amnesia induced by the muscarinic antagonist scopolamine (0.25 mg/kg). We found that thioperamide exerted a dose-dependent facilitative effect on memory consolidation. Furthermore, the H3 receptor antagonist reversed scopolamine- and especially dizocilpine-induced amnesia. The results strongly support the view that the brain mechanisms of memory consolidation involve a functional interaction between the NMDA and the H3 sites. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailBehavioral characterization of acetaldehyde in C57BL/6J mice: locomotor, hypnotic, anxiolytic and amnesic effects
Quertemont, Etienne ULiege; Tambour, Sophie ULiege; Bernaerts, Pascale et al

in Psychopharmacology (2004), 177(1-2), 84-92

Rationale: Acetaldehyde, the first metabolite of ethanol, was recently suggested to contribute to many behavioral effects of ethanol, although few studies have directly investigated the behavioral effects ... [more ▼]

Rationale: Acetaldehyde, the first metabolite of ethanol, was recently suggested to contribute to many behavioral effects of ethanol, although few studies have directly investigated the behavioral effects of acetaldehyde itself. Objectives: The aim of the present study was to characterize the locomotor, hypnotic, anxiolytic-like and amnesic effects of acetaldehyde in C57BL/6J mice. Methods: Increasing doses of acetaldehyde (0 - 300 mg/kg) were injected intraperitoneally and their effects on a series of representative behaviors were investigated. The locomotor effects of acetaldehyde were measured in activity boxes. The duration of the loss of righting reflex was used as an index of the hypnotic effects of acetaldehyde. The anxiolytic-like effects of acetaldehyde were tested with an elevated plus-maze and the amnesic effects with the one-trial passive avoidance test. Finally, brain and blood acetaldehyde concentrations were assessed. Results: Acetaldehyde induced a significant hypolocomotor effect at 170 mg/kg and higher doses. In addition, the hypnotic effects of acetaldehyde were demonstrated by a loss of righting reflex after the administration of 170 and 300 mg/kg acetaldehyde. The elevated plus-maze showed that acetaldehyde does not possess anxiolytic-like properties. Finally, acetaldehyde ( 100 - 300 mg/kg) dose-dependently altered memory consolidation as shown by a reduced performance in the passive avoidance test. Conclusions: The present results show that acetaldehyde induces sedative, hypnotic and amnesic effects, whereas it is devoid of stimulant and anxiolytic-like properties in C57BL/6J mice. However, the behavioral effects of acetaldehyde after intraperitoneal administration were apparent at very high brain concentrations. The present results also indicate that acetaldehyde is unlikely to be involved in the anxiolytic properties of ethanol in mice. [less ▲]

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See detailResponse to novelty as a predictor for drug effects: the pitfalls of some correlational studies
Quertemont, Etienne ULiege; Brabant, Christian ULiege; Tirelli, Ezio ULiege

in Psychopharmacology (2004), 173(1-2), 221-224

In recent years, an individual's response to novelty has been postulated to predict its response to drugs of abuse and particularly to their addictive properties (Piazza et al. 1990). The hypothesis of a ... [more ▼]

In recent years, an individual's response to novelty has been postulated to predict its response to drugs of abuse and particularly to their addictive properties (Piazza et al. 1990). The hypothesis of a relationship between the response to novelty and the effects of addictive drugs was supported by a number of animal studies that reported correlations between responses to a novel environment and various effects of drugs, such as their locomotor stimulant effects, their reinforcing action or their propensity to be self-administered (Piazza et al. 1990; Klebaur et al. 2001; Carey et al. 2003; Shimosato and Watanabe 2003). Most of these studies concluded that an animal's response to novelty predicts its subsequent response to drug administration. However, correlational studies are sometimes hampered by methodological and statistical weaknesses that preclude a proper interpretation of the results. The two most frequent weaknesses are the lack of consideration for the correlation in the control group and the calculation of spurious correlations. [less ▲]

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See detailBehavioral characterization of acetaldehyde in mice
Quertemont, Etienne ULiege; Tambour, Sophie ULiege; Tirelli, Ezio ULiege

in Alcoholism, Clinical & Experimental Research (2004), 28(5), 196-196

Acetaldehyde, the first product of ethanol metabolism, has long been speculated to be involved in many of the behavioral effects of ethanol, although its precise role remains a matter of debate. However ... [more ▼]

Acetaldehyde, the first product of ethanol metabolism, has long been speculated to be involved in many of the behavioral effects of ethanol, although its precise role remains a matter of debate. However, most of the results supporting a role for acetaldehyde in ethanol’s effects come from studies in which ethanol metabolism was pharmacologically manipulated, whereas the behavioral properties of acetaldehyde itself are still largely unknown. In the present studies, we have characterized the locomotor, hypnotic, anxiolytic and amnesic effects of both ethanol and acetaldehyde in C57BL/6J and CD1 mice. Several classical behavioral tests were used: the open field, the loss of righting reflex, the plus-maze, the place conditioning and the passive avoidance. The results show that acetaldehyde similarly to ethanol induces sedation and hypnotic effects at high doses. In addition, acetaldehyde displays potent amnesic effects in the passive avoidance test, suggesting that the first metabolite of ethanol might be critically involved in the memory-impairing effects of ethanol. However, in contrast to ethanol, acetaldehyde does not show anxiolytic properties in the plus-maze. In a second part of the present studies, acetaldehyde contribution to ethanol’s behavioral effects was investigated by using several inhibitors of ethanol metabolism (3-amino-1,2,4-triazole, a catalase inhibitor, and disulfiram, an aldehyde dehydrogenase inhibitor). Overall, the present results suggest that acetaldehyde is involved in some of ethanol’s behavioral effects (amnesia, locomotor depression, sedation) but not in others (in particular anxiolysis). [less ▲]

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See detailThe magnitude and the extinction duration of the cocaine-induced conditioned locomotion-activated response are related to the number of cocaine injections paired with the testing context in C57BL/6J mice
Michel, Anne; Tambour, Sophie ULiege; Tirelli, Ezio ULiege

in Behavioural Brain Research (2003), 145(1-2), 113-123

Behavioural activation repeatedly induced by a stimulant in rodents can persist in the absence of the drug if the animals are tested in the context where the drug was previously given, a phenomenon often ... [more ▼]

Behavioural activation repeatedly induced by a stimulant in rodents can persist in the absence of the drug if the animals are tested in the context where the drug was previously given, a phenomenon often explained in terms of Pavlovian conditioning. The aim of this study was to verify whether the amplitude of the putative CR (the drug-like activity) increases with the number of the US-CS associations (the number of drug-context pairings), one of the most representative rules of Pavlovian conditioning. The effect of the number of trials on the speed of extinction was also considered. C57BL/6J mice received 3, 6 or 12 once-daily injections of either saline or 12 mg/kg (-)-cocaine hydrochloride (s.c.) in the same test context, a photocell activity-box in which they were tested for 60 min after every injection. Other groups received the same treatments outside of the test context (being placed in a novel cage tub after each injection). Twenty-four hours after the last treatment session, all mice were challenged with saline in the test context (test for conditioned activity), extinction sessions taking place on the three subsequent days. Sensitisation to the locomotor-activating effect of cocaine developed only amongst the animals injected 6 or 12 times, the magnitude of the last sensitised response being comparable for these two injections regimen. On saline challenge, only the animals that had received 6 or 12 cocaine injections showed significant conditioned activity (CR), with the greatest response occurring following 12 injections. The 6-trial group reached the level of non-significance after fewer extinction sessions than the 12-trial group; however, the rates of extinction did not differ (comparable regression coefficients and quasi-parallel curves). These results suggest that the amplitude of the CR (cocaine-like stimulation after saline), and perhaps less convincingly the duration of extinction, are functions of the number of the US-CS (cocaine-context) pairings, supporting the Pavlovian nature of post-sensitisation placebo drug-like effects. (C) 2003 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailGabazine (SR95531) effect on memory consolidation and context-dependent memory in mice
Bernaerts, R.; Tirelli, Ezio ULiege

in Behavioural Pharmacology (2003, September), 14(Suppl. 1), 29

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