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

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 ULg; Tambour, Sophie ULg; 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 ULg; Brabant, Christian ULg; Tirelli, Ezio ULg

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 ULg; Tambour, Sophie ULg; Tirelli, Ezio ULg

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 ULg; Tirelli, Ezio ULg

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 ULg

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

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See detailInfluence of dose on the persistence of conditioned place preference induced by cocaine in C57BL/6J mice
Brabant, Christian ULg; Tirelli, Ezio ULg

in Behavioural Pharmacology (2003, September), 14(Suppl. 1), 54

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See detailSensitised locomotion does not predict conditioned locomotion in cocaine-treated mice: further evidence against the excitatory conditioning model of context-dependent sensitisation
Tirelli, Ezio ULg; Tambour, Sophie ULg; Michel, Anne

in European Neuropsychopharmacology (2003), 13(4), 289-296

The excitatory conditioning model of contextual sensitisation proposes that the progressive emergence of the locomotion-activating effect of cocaine (or any other stimulant drug) characterising that ... [more ▼]

The excitatory conditioning model of contextual sensitisation proposes that the progressive emergence of the locomotion-activating effect of cocaine (or any other stimulant drug) characterising that phenomenon is due to a growing conditioned response (the test context cues) that mimics the unchanging unconditioned response (the drug effect). The present study aimed at verifying whether the relationship between the amplitude of sensitisation and the size of the conditioned response was positive, a direct implication of that view. Sensitisation to the locomotion-activating effect of cocaine (10 mg/kg, s.c.) was firstly generated over 10 daily sessions in 25 mice (strain C57131/6J), another lot of 25 mice receiving the same dose of cocaine outside of the testing context. Conditioned locomotion was assessed 24 h later. No significant linear correlations were found between the magnitude of the conditioned response and the magnitude of the sensitised response (delta scores), the rate of sensitisation (individual regression coefficients) or the magnitude of the initial unconditioned response to cocaine (scores in the first session of sensitisation treatment). Accordingly, there was no significant correlation between the magnitude of the initial unconditioned response and the magnitude of the sensitised response or that of the initial unconditioned response. Therefore, the conditioned response is neither necessary nor sufficient for the development of context-dependent sensitisation of the locomotion-activating effect of cocaine, a conclusion that refutes the excitatory conditioning model of that chronic effect. (C) 2003 Elsevier B.V./ECNP. All rights reserved. [less ▲]

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See detailFacilitatory effect of the dopamine D4 receptor agonist PD168,077 on memory consolidation of an inhibitory avoidance learned response in C57BL/6J mice
Bernaerts, P.; Tirelli, Ezio ULg

in Behavioural Brain Research (2003), 142(1-2), 41-52

The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870 ... [more ▼]

The still unknown contribution of the D4 receptors to memory consolidation was studied examining the memory effects of the dopamine D4 agonist PD168,077, the putative dopamine D4 antagonist L745,870, their mutual combination, and the combination of the D4 agonist with representative compounds acting as agonist or antagonist on the D1, D2 and the D3 receptors. 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 24h later. PD168,077 (0.5-10mg/kg) dose-dependently improved memory performance and L745,870 (0.05-5mg/kg) at doses lower than 1mg/kg increased and at doses higher than 1mg/kg impaired memory performance. PD168,077 did not affect the paradoxical promnesic effect of low doses (0.1-0.5mg/kg) of L745,870, but antagonised the memory-impairing effect induced by 5mg/kg L745,870. The D1 antagonist SCH23390 (0.025-0.05 mg/kg) and the D2 antagonist eticlopride (0.01-0.05 mg/kg) antagonised the promnesic effects of PD168,077, which attenuated the decreasing effect on memory consolidation of both D1 and D2 antagonists. Accordingly, the D1 agonist SKF38393 (5-20mg/kg) and the D2 agonist quinelorane (0.1-1 mg/kg) both synergistically magnified the memory-improving effects of the D4 agonist. The dopamine D3 antagonist U99194A (2.5-10mg/kg) did not affect the promnesic effects induced by the D4 agonist, which nevertheless abolished the U99194A-induced promnesic effects. Additionally, the amnesic effects produced by the D3 agonist 7-OH-DPAT (0.01-1 microg/kg) was attenuated by PD168,077. These results suggest a potential role of dopamine D4 receptors in memory consolidation, which would be similar to that of the D1 and D2 receptors and probably opposite to that of the D3 receptors. [less ▲]

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See detailQuasi-asymptotic development of conditioned hyperactivity induced by intermittent injections of cocaine in C57BL/6J mice
Brabant, Christian ULg; Tambour, Sophie ULg; Tirelli, Ezio ULg

in Pharmacology, Biochemistry & Behavior (2003), 75(2), 273-280

The emergence of a conditioned cocaine-induced hyperlocomotion was examined in C57BL/6J mice using a procedure that has not been used previously. Two days after a session of preexposure to the test ... [more ▼]

The emergence of a conditioned cocaine-induced hyperlocomotion was examined in C57BL/6J mice using a procedure that has not been used previously. Two days after a session of preexposure to the test chambers under saline, a first group of mice (cocaine-cued) received five once-daily injections of 10-mg/kg sc cocaine every other day (on the odd days of the chronic treatment period) and a saline injection on the 5 days following each cocaine injection day (on the even days of the treatment period), in all cases before being placed in the test chamber. Another group of mice (saline-cued) received 10 injections of saline on both the even and the odd days in the same context, and a third group of mice (cocaine-uncued) received five injections of saline on the even days in the test context and five injections of cocaine on the odd days in an alternative context. On the odd days sessions, the cocaine-cued group showed significant repeated increases in locomotion without behavioural sensitisation being induced, whereas the saline-cued levels of locomotion remained on baseline levels. On the first even session, the three groups did not differ from each other and showed lower levels of locomotion than on the preexposure session. During the two following even sessions, the cocaine-cued group showed an increase in locomotion that levelled off on the two remaining sessions, whereas the saline-cued and the cocame-uncued groups (which presented comparable values) exhibited significantly lower levels of locomotion. That pattern of successive placebo responses resembles the typical S-shaped development of a Pavlovian conditioned response, albeit the increase described here was quite rapid. The protocol used here may provide an additional method for the experimental analysis of stimulant-induced conditioned placebo activity. (C) 2003 Elsevier Science Inc. All rights reserved. [less ▲]

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See detailOntogenesis of behavioral sensitization and conditioned place preference induced by psychostimulants in laboratory rodents
Tirelli, Ezio ULg; Laviola, Giovanni; Adriani, Walter

in Neuroscience & Biobehavioral Reviews (2003), 27(1-2), 163-178

The present review deals mainly with the ontogenesis of two important phenomena involved in vulnerability to several neuropsychiatric disorders, namely with drug-induced sensitization (both contextual and ... [more ▼]

The present review deals mainly with the ontogenesis of two important phenomena involved in vulnerability to several neuropsychiatric disorders, namely with drug-induced sensitization (both contextual and non-contextual) and with conditioned place preference. The term 'infancy' covers the first three postnatal weeks during development in rats and mice. Conversely, the term 'adolescence' may cover the whole postnatal period ranging from weaning (PND 21) to adulthood (at least PND 60) or specifically the period around the onset of puberty (animals aged 33-44 days). Recent studies in rats demonstrated that the establishment of a context-dependent sensitization appears during the first (for repeated drug administration) or during the second (for a single drug administration) postnatal week. However, the memory of drug-context association is transient in developing pups (lasting one or two days following the drug pretreatment). The long-term retention of drug-context associations matures progressively, and is complete by the third week of postnatal life. Finally, those mechanisms responsible for an adult-like profile of context-independent pharmacological sensitization appear later during ontogenesis, being mature by the fourth week of postnatal life. Another set of experiments extended this ontogenetic characterization by comparing adolescent and adult mice. When compared to the latter, the former subjects exhibit a greater amphetamine-induced locomotor sensitization, almost no sensitization of aversive stereotyped behaviors, and a less marked place conditioning. The strength of the drug-induced place conditioning was also directly compared with the unconditioned novelty-seeking drive. In conclusion, neonatal rats are able to show a relatively short-lasting retention of sensitized drug effects (short-term sensitization), whereas the ability to exhibit relatively long-lasting sensitized effects matures progressively during infancy (long-term sensitization). On the other hand, adolescent mice show a reduced sensitization of drug-induced psychotic symptoms, together with a more marked sensitization of arousing and euphorigenic properties of the drug and a reduced incentive memory of its hedonic effects. These age-related changes do imply very different degrees of vulnerability to drug addiction and several other neuropsychiatric disorders. (C) 2003 Elsevier Science Ltd. All rights reserved. [less ▲]

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See detailBehavioral characterization of acetaldehyde in C57BL/6J mice: Locomotor, hypnotic and ataxic effects
Quertemont, Etienne ULg; Tambour, Sophie ULg; Tirelli, Ezio ULg

in Behavioural Pharmacology (2003), 14(Suppl. 1), 69-69

Acetaldehyde, the first ethanol metabolite, was recently suggested to play a major role in many behavioral effects of ethanol. However, no studies have directly investigated the behavioral effects of ... [more ▼]

Acetaldehyde, the first ethanol metabolite, was recently suggested to play a major role in many behavioral effects of ethanol. However, no studies have directly investigated the behavioral effects of acetaldehyde after acute administration. Therefore, the aim of the present study was to characterize the locomotor, hypnotic and ataxic effects of acetaldehyde in C57BL/6J mice. Various acetaldehyde doses (0-300 mg/kg) were injected intraperitoneally and their effects were investigated with several classical behavioral tests. The locomotor effects of acetaldehyde were measured in standard activity boxes. In addition, the loss of righting reflex was used to assess the hypnotic effects of acetaldehyde. Finally, the ataxic effects of acetaldehyde were studied with the horizontal wire test. The results show that acetaldehyde induced a significant hypolocomotor effect at 170 mg/kg and higher doses. In addition, the hypnotic effects of acetaldehyde were evidenced by a loss of righting reflex in doses between 170 and 300 mg/kg. However, the locomotor and hypnotic effects of acetaldehyde were very brief relative to what is observed after ethanol administration. After 170 mg/kg acetaldehyde, normal activity was recovered in less than 30 minutes and the loss of righting reflex lasted only an average of 6.14 ± 1.29 minutes after the administration of 300 mg/kg acetaldehyde, the highest testable dose before lethality. Ataxic effects were observed with lower doses that did not significantly affect locomotor activity. These results show that acetaldehyde, like ethanol, possesses sedative, hypnotic and ataxic properties and therefore indicate that the first product of ethanol metabolism might be involved in these ethanol effects. [less ▲]

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See detailBehavioral characterization of acetaldehyde in C57BL/6J mice: Anxiolytic, amnesic and hedonic effects
Tambour, Sophie ULg; Quertemont, Etienne ULg; Tirelli, Ezio ULg

in Behavioural Pharmacology (2003), 14(Suppl. 1), 68-69

It has been postulated that a number of central effects of ethanol are mediated through the action of its first metabolite, acetaldehyde. In particular, acetaldehyde might be involved in the anxiolytic ... [more ▼]

It has been postulated that a number of central effects of ethanol are mediated through the action of its first metabolite, acetaldehyde. In particular, acetaldehyde might be involved in the anxiolytic and hedonic effects of ethanol and is therefore believed to play an important role in alcohol abuse. In agreement with this assumption, previous studies indicated that acetaldehyde is mainly reinforcing in rats, which have been shown to readily self-administer acetaldehyde both peripherally and centrally. However, the hedonic effects of acetaldehyde have never been tested in mice, and the possible amnesic and anxiolytic effects of acetaldehyde remain to be elucidated. Therefore, the present studies were aimed at characterizing the anxiolytic, hedonic and amnesic effects of acetaldehyde after its acute peripheral administration to C57BL/6J mice. The effects of intraperitoneal acetaldehyde (0-300 mg/kg) injections were assessed in several classical behavioral tests. The anxiolytic effects were tested with the elevated plus maze, the hedonic effects with the place conditioning procedure and the amnesic effects with the passive avoidance apparatus. Our results show that acetaldehyde dose-dependently altered memory consolidation as evidenced by a reduced performance in the passive avoidance test when acetaldehyde was injected immediately after training at doses between 100 and 300 mg/kg. The elevated plus-maze showed that acetaldehyde, in contrast to ethanol, does not possess anxiolytic properties. Finally, the results of the place conditioning experiment confirmed that acetaldehyde displays significant hedonic properties. The present results add further support to the role of acetaldehyde in ethanol amnesic and hedonic effects but interestingly suggest that acetaldehyde is not involved in ethanol anxiolytic effects. [less ▲]

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See detailEffects of the social conditions of housing through testing on cocaine-induced contextual sensitisation and conditioned locomotion in C57BL/6J mice
Michel, Alexa ULg; Tirelli, Ezio ULg

in Progress in Neuro-Psychopharmacology & Biological Psychiatry (2002), 26(6), 1185-1191

The potential differential effects of isolated and collective housing through the testing phase on sensitisation to cocaine-induced locomotion, the subsequent conditioned locomotion and the context ... [more ▼]

The potential differential effects of isolated and collective housing through the testing phase on sensitisation to cocaine-induced locomotion, the subsequent conditioned locomotion and the context-dependent expression of sensitisation were examined in C57BL/6J male mice. [less ▲]

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See detailPost-sensitisation conditioned hyperlocomotion induced by cocaine is augmented as a function of dose in C57BL/6J mice
Michel, Alexa ULg; Tirelli, Ezio ULg

in Behavioural Brain Research (2002), 132(2), 179-186

The study tested the possibility of a positive relationship between the dose of cocaine and the size of the placebo effect generated after contextual sensitisation to the behavioural effects of cocaine ... [more ▼]

The study tested the possibility of a positive relationship between the dose of cocaine and the size of the placebo effect generated after contextual sensitisation to the behavioural effects of cocaine. Male C57BL/6J mice were first injected (subcutaneous, s.c.) over seven successive daily sessions with saline or one of three doses of cocaine (2.5, 5 or 7.5 mg/kg), either in the test room or in the colony room (before being placed in a novel cage tub). On the test day, 24 h after chronic pre-treatment, mice from the four conditions were challenged under saline in the test room. Mice were video-recorded and their behaviours were scored using a time-sampling technique. A dose-dependent development of sensitisation was first generated. On the saline challenge test day, significant levels of placebo hyperlocomotion were obtained for mice previously given 5 and 7.5 mg/kg, but not 2.5 mg/kg cocaine, the effect being significantly greater in the mice pretreated with the highest dose than in those receiving the intermediate one, which exhibited a placebo effect that was greater than that of the mice pretreated with 2.5 mg/kg cocaine. Therefore, the magnitude of the placebo effect was a function of the intensity of the unconditioned stimulus (the dose used to generate sensitisation). Such results directly support the Pavlovian conditioning account of post-sensitisation placebo effects. [less ▲]

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See detailConditioned hyperkinesia induced by cocaine in mice is dose-dependent but not correlated with the unconditioned response or the contextually-sensitized response
Michel, Alexa ULg; Tirelli, Ezio ULg

in Behavioural Pharmacology (2002), 13(1), 59-71

The aims of the study were to test whether drug dose is positively related to the magnitude of the conditioned response following sensitization to the behavioural effects of cocaine and to investigate the ... [more ▼]

The aims of the study were to test whether drug dose is positively related to the magnitude of the conditioned response following sensitization to the behavioural effects of cocaine and to investigate the relationship between the conditioned response and cocaine-induced sensitization. Male mice (C57BL/6J) were first injected over seven successive days with either saline or cocaine at 2.5, 5, 10 or 20 mg/kg s.c., in the testing room. On the test day, 24 h after the last injection, mice from all conditions were challenged with saline in the testing room to test for conditioned cocaine effects. Mice were video-recorded and various behaviours were later scored using a time-sampling technique. Cocaine-elicited orofacial stereotypy was significantly sensitized at the two highest doses and dose-dependently conditioned at the three highest doses. Cocaine-increased locomotion was sensitized at the three highest doses and significantly conditioned at 10 and 20 mg/kg. Cocaine-increased sniffing did not change over pretreatment at any dose, and was conditioned only at 10 mg/kg. Cocaine-decreased immobility also did not change over pretreatment at any dose, but was conditioned at 10 and 20 mg/kg. Concomitantly, rearing was reduced by cocaine at 10 and 20 mg/kg, without sensitization being induced, and it was reduced under saline challenge after 5 mg/kg cocaine, while cocaine-decreased grooming was sensitized at the three highest doses and conditioned at 10 and 20 mg/kg cocaine. There was a positive relation between the size of the conditioned response for orofacial stereotypy and the magnitude of the unconditioned stimulus (the doses), a result conforming to the Pavlovian account of the placebo effect. This could also be concluded from considering the behaviour patterns as components of a unique placebo effect (hyperkinetic syndrome), since orofacial stereotypy, very apparent at 20 mg/kg cocaine, interfered at that dose with the full-blown expression of locomotion and sniffing, both yielding (approximately) inverted U-shaped dose-effect curves. However, no correlation was found between the magnitude of the conditioned response and the amplitude of sensitization (the difference between the initial unconditioned non-sensitized response and the last unconditioned sensitized response), a finding which indicates that conditioned responding does not participate in the generation of the sensitized effects, contrary to the 'excitatory conditioning model of contextual sensitization' [less ▲]

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See detailDay-by-day maturation of the long-term expression of cocaine sensitization acquired before weaning in the rat
Tirelli, Ezio ULg

in Behavioral Neuroscience (2001), 115(5), 1101-1110

This study aimed to identify the ontogenetic period during which long-term expression of behavioral sensitization to cocaine begins to emerge. Rat pups aged 4, 8, 12, or 16 days received a pretreatment of ... [more ▼]

This study aimed to identify the ontogenetic period during which long-term expression of behavioral sensitization to cocaine begins to emerge. Rat pups aged 4, 8, 12, or 16 days received a pretreatment of 4 daily injections of 15 mg/kg sc cocaine paired with the test chamber for 45 min. Pups were then tested for sensitization in that context after abstinence intervals ranging from 2 to 10 days. On test days, pups were videotaped, and their behavior was scored later. Sensitization was detected after intervals of 2, 4, 5, or 9 days in pups aged 4-7, 8-11, 12-15, or 16-19 days during pretreatment, respectively. These results suggest that the mechanisms for long-term retention of sensitization mature incrementally in the rat, starting to emerge gradually after the I st week of age, whereas those relevant to short-term retention and initiation of sensitization are present earlier. [less ▲]

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