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See detailHigher long-lasting ethanol sensitization after adolescent ethanol exposure in mice
Quoilin, Caroline; Didone, Vincent ULg; Tirelli, Ezio ULg et al

in Psychopharmacology (2014), 231

Rationale. Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is ... [more ▼]

Rationale. Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is a possible consequence of ethanol exposure during adolescence. Objectives. The aim of this study was to characterize the long-term alterations in the stimulant effects of ethanol and in the rate of ethanol sensitization in mice pre-exposed to ethanol during adolescence in comparison to mice pre-exposed to ethanol in adulthood. Methods. Adolescent and adult female SWISS mice were injected with saline or ethanol (2.5 or 4 g/kg) during 14 consecutive days. After a three weeks period of ethanol abstinence, mice were tested as adults before and after a second exposure to daily repeated ethanol injections. Results. All mice pre-exposed to ethanol as adults or adolescents showed higher stimulant effects when re-exposed to ethanol three weeks later. However, this enhanced sensitivity to the stimulant effects of ethanol was of significantly higher magnitude in mice repeatedly injected with high ethanol doses (4g/kg) during adolescence. Furthermore, the increased expression of ethanol stimulant effects in these mice was maintained even after a second procedure of ethanol sensitization. Conclusions. Adolescence is a critical period for the development of a sensitization to ethanol stimulant properties providing that high intermittent ethanol doses are administered. These results might contribute to explain the relationship between age at first alcohol use and risks of later alcohol problems and highlight the dangers of repeated consumption of high alcohol amounts in young adolescents. [less ▲]

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See detailDevelopmental differences in ethanol-induced sensitization using postweanling, adolescent, and adult Swiss mice
Quoilin, Caroline ULg; Didone, Vincent ULg; Tirelli, Ezio ULg et al

in Psychopharmacology (2012), 219

Rationale: The maturing adolescent brain has been suggested to be more sensitive than the adult brain to ethanol-induced neuroadaptations. In animal studies, sensitization to the stimulant effects of ... [more ▼]

Rationale: The maturing adolescent brain has been suggested to be more sensitive than the adult brain to ethanol-induced neuroadaptations. In animal studies, sensitization to the stimulant effects of ethanol is used to study the vulnerability to chronic ethanol-induced neurobehavioral alterations. Objectives: The aim of the present study was to systematically characterize age-dependent changes in the development and expression of the sensitization to the stimulant effects of a range of ethanol doses in female Swiss mice. Three ages were studied: 21-day-old mice (postweanlings), 35-day-old mice (adolescents), and 63-day-old mice (adults). Methods: Postweanling, adolescent, and adult mice were daily injected with saline or various ethanol doses (1.5 to 4 g/kg) for 7 days. They were then tested for acute and sensitized locomotor activity. Results: Postweanling and adolescent mice were more sensitive than adult mice to the acute stimulant effects of ethanol. In adult mice, daily injections of ethanol at doses between 2.5 and 4 g/kg led to significant sensitization. Higher ethanol doses (3.5 and 4 g/kg) were required to induce sensitization in postweanling and adolescent mice. However, younger mice showed ethanol sensitization of higher magnitude. Conclusions: Young mice develop very strong ethanol sensitization at doses that mimic binge drinking in humans. These results might explain why early ethanol drinking during adolescence is related to a higher prevalence of subsequent alcohol disorders. [less ▲]

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See detailOntogeny of the stimulant and sedative effects of ethanol in male and female Swiss mice: gradual changes from weaning to adulthood
Quoilin, Caroline ULg; Didone, Vincent ULg; Tirelli, Ezio ULg et al

in Psychopharmacology (2010), 212(4), 501-512

Rationale: The adolescent period is characterized by a specific sensitivity to the effects of alcohol, which is believed to contribute to the enhanced risks of alcohol dependence when drinking is ... [more ▼]

Rationale: The adolescent period is characterized by a specific sensitivity to the effects of alcohol, which is believed to contribute to the enhanced risks of alcohol dependence when drinking is initiated early during adolescence. In adolescent rodents, while the reduced sensitivity to the sedative effects of ethanol has been well characterized, its stimulant effects have not yet been extensively studied. Objectives: The present study characterized the development of the stimulant and sedative effects of acute ethanol in male and female Swiss mice from weaning to early adulthood and tested whether both effects are interrelated. Methods: In a first experiment, mice aged 21, 28, 35, 42 and 60 days were injected with various ethanol doses and tested for ethanol-induced locomotor activity. In an independent experiment, mice of the same groups of age were injected with 4 g/kg ethanol and ethanol-induced sedation was quantified with the loss of righting reflex procedure. Results: In male and female mice, the stimulant effects of ethanol gradually decreased, whereas its sedative effects increased with age. When the sedation was statistically controlled using a covariance analysis, the differences between adult and juvenile mice in the locomotor stimulation were significantly reduced. Conclusions: From weaning to early adulthood, the acute stimulant and sedative effects of ethanol show gradual changes that are similar in male and female mice. Although the initial tolerance to the sedative effects of ethanol contribute to the changes in ethanol-induced locomotor activity, young mice also show a higher sensitivity to the stimulant effects of ethanol. [less ▲]

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See detailEffects of the H(3) receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions.
Brabant, Christian ULg; Alleva, Livia ULg; Grisar, Thierry ULg et al

in Psychopharmacology (2009), 202(4), 673-87

RATIONALE: Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H(3) receptor inverse agonist that enhances histamine release in the brain, potentiate cocaine ... [more ▼]

RATIONALE: Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H(3) receptor inverse agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice. MATERIALS AND METHODS: We investigated whether immepip, a selective H(3) agonist, could reverse the potentiating effects of thioperamide. Moreover, the non-imidazole H(3) inverse agonist A-331440 was tested on the locomotor effects of cocaine. Using high-performance liquid chromatography with ultraviolet detection, cocaine plasma concentrations were measured to study potential drug-drug interactions between thioperamide and cocaine. Finally, thioperamide was tested on the locomotor effects of cocaine in histamine-deficient knockout mice in order to determine the contribution of histamine to the modulating effects of thioperamide. RESULTS: Thioperamide potentiated cocaine-induced hyperlocomotion in normal mice, and to a higher extent, in histamine-deficient knockout mice. A-331440 only slightly affected the locomotor effects of cocaine. Immepip did not alter cocaine-induced hyperactivity but significantly reduced the potentiating actions of thioperamide on cocaine's effects. Finally, plasma cocaine concentrations were more elevated in mice treated with thioperamide than in mice that received cocaine alone. CONCLUSIONS: The present results indicate that histamine released by thioperamide through the blockade of H(3) autoreceptors is not involved in the ability of this compound to potentiate cocaine induced-hyperactivity. Our data suggest that thioperamide, at least at 10 mg/kg, increases cocaine-induced locomotion through the combination of pharmacokinetic effects and the blockade of H(3) receptors located on non-histaminergic neurons. [less ▲]

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See detailParametric analysis of the development and expression of ethanol-induced behavioral sensitization in female Swiss mice: effects of dose, injection schedule, and test context.
Didone, Vincent ULg; Quoilin, Caroline ULg; Tirelli, Ezio ULg et al

in Psychopharmacology (2008), 201(2), 249-60

RATIONALE: Repeated administrations of ethanol induce a progressive and enduring increase in its locomotor stimulant effects, a phenomenon termed behavioral sensitization that has not been systematically ... [more ▼]

RATIONALE: Repeated administrations of ethanol induce a progressive and enduring increase in its locomotor stimulant effects, a phenomenon termed behavioral sensitization that has not been systematically characterized. OBJECTIVE: The aim of the present studies was to characterize the development and expression of ethanol sensitization in female Swiss mice by examining (1) the doses of ethanol that induce behavioral sensitization, (2) the doses of acute ethanol challenges that are necessary to express behavioral sensitization, (3) the effects of the intervals between administrations, and (4) the context dependency of ethanol sensitization. MATERIALS AND METHODS: Mice were i.p. injected for 8 days with various ethanol doses, and locomotion was recorded for 5 min. Two days after the last sensitization session, ethanol sensitization was tested in 30-min test sessions. RESULTS: Mice repeatedly injected with 2.5 g/kg ethanol showed a progressive (200-300%) increase in locomotor activity. In response to a 2.5 g/kg ethanol challenge, the mice repeatedly treated with doses above 1.5 g/kg showed a significant sensitization. Following the induction of sensitization with the maximally effective sensitizing dose (2.5 g/kg), mice showed greater activation after challenges with 1.5, 2.0, 2.5, and 3.0 g/kg ethanol. The intervals (24, 48, or 96 h) between ethanol injections did not affect the induction or expression of sensitization. Finally, sensitization to 2.5 g/kg ethanol was expressed regardless of the context in which it was induced. CONCLUSIONS: Female Swiss mice develop a robust context-independent sensitization after repeated ethanol injections at all doses above 1.5 g/kg, including highly sedative doses such as 4 g/kg. [less ▲]

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See detailThe psychostimulant and rewarding effects of cocaine in histidine decarboxylase knockout mice do not support the hypothesis of an inhibitory function of histamine on reward
Brabant, Christian ULg; Quertemont, Etienne ULg; Anaclet, Christelle et al

in Psychopharmacology (2007), 190(2), 251-263

RATIONALE AND OBJECTIVES: Lesion studies have shown that the tuberomammillary nucleus (TM) exerts inhibitory effects on the brain reward system. To determine whether histamine from the TM is involved in ... [more ▼]

RATIONALE AND OBJECTIVES: Lesion studies have shown that the tuberomammillary nucleus (TM) exerts inhibitory effects on the brain reward system. To determine whether histamine from the TM is involved in that reward inhibitory function, we assessed the stimulant and rewarding effects of cocaine in knockout mice lacking histidine decarboxylase (HDC KO mice), the histamine-synthesizing enzyme. If histamine actually plays an inhibitory role in reward, then it would be expected that mice lacking histamine would be more sensitive to the behavioral effects of cocaine. MATERIALS AND METHODS: The first experiment characterized spontaneous locomotion and cocaine-induced hyperactivity (0, 8, and 16 mg/kg, i.p.) in wild-type and HDC KO mice. The rewarding effects of cocaine were investigated in a second experiment with the place-conditioning technique. RESULTS: The first experiment demonstrated that histidine decarboxylase mice showed reduced exploratory behaviors but normal habituation to the test chambers. After habituation to the test chambers, HDC KO mice were slightly, but significantly, less stimulated by cocaine than control mice. This finding was replicated in the second experiment, when cocaine-induced activity was monitored with the place-conditioning apparatus. Furthermore, a significant place preference was present in both genotypes for 8 and 16 mg/kg cocaine, but not for 2 and 4 mg/kg. CONCLUSIONS: Our data confirm previous results demonstrating that HDC KO mice show reduced exploratory behaviors. However, contrary to the hypothesis that histamine plays an inhibitory role in reward, histamine-deficient mice were not more responsive to the psychostimulant effects of cocaine. [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 ULg; Quertemont, Etienne ULg; Tirelli, Ezio ULg

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 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 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 detailBrain ethanol concentrations and ethanol discrimination in rats : effects of dose and time
Quertemont, Etienne ULg; Green, Heather L.; Grant, Kathleen A.

in Psychopharmacology (2003), 168(3), 262-270

Rationale. In drug discrimination procedures, the substitution pattern for ethanol of various receptor ligands is dependent upon ethanol training dose, presumably reflecting functionally different ... [more ▼]

Rationale. In drug discrimination procedures, the substitution pattern for ethanol of various receptor ligands is dependent upon ethanol training dose, presumably reflecting functionally different concentrations of ethanol in the brain. The discriminative stimulus effects of ethanol are also time-dependent, although very few studies have investigated the time course of ethanol discriminations. Objectives. The present study investigated the relationship between brain ethanol concentrations (BrEC), as measured by intracranial microdialysis of the nucleus accumbens, and the time course of ethanol discriminative effects. Methods. Two groups of rats were trained to discriminate either 1.0 or 2.0 g/kg ethanol from water following a 30-min post-ethanol interval. Following training, the time course of the discriminative stimulus was assessed using a series of abbreviated testing trials at 20-min intervals for 5 h after the administration of various ethanol doses (0, 0.5, 1.0 and 2.0 g/kg). The rats were then fitted with microdialysis probes and the time course of BrECs were determined under conditions similar to the behavioral assessments. Results. BrECs were significantly above zero at 4 min post-gavage and attained peak concentrations of 16 mmol/l, 24 mmol/l and 42 mmol/l at 9 min, 16 min and 95 min after IG administration of 0.5, 1.0 and 2.0 g/kg ethanol, respectively. BrECs were similar in ethanol-naive and ethanol-trained rats, indicating a lack of pharmacokinetic tolerance under these discrimination procedures. The discriminative stimulus effects of ethanol were dose- and time-dependent, with a threshold concentration of approximately 12 mmol/l achieved at 5 min after 1.0 g/kg ethanol gavage in rats trained to discriminate 1.0 g/kg ethanol. Acute tolerance to the discriminative stimulus effects of ethanol was evident from BrECs 2-5 h post-ethanol gavage. Conclusions. Ethanol given intragastrically results in a rapid increase in BrEC, independent of ethanol exposure history. The discriminative stimulus effects of ethanol trained at 30 min post-gavage reflect a specific range of BrEC, and depend on the training dose. These data suggest that qualitatively different stimulus effects of ethanol reflect both different ranges of BrEC, as well as within dose acute tolerance to the discriminative stimulus effects. [less ▲]

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See detailRole of acetaldehyde in ethanol-induced conditioned taste aversion in rats
Escarabajal, Dolores M.; De Witte, Philippe; Quertemont, Etienne ULg

in Psychopharmacology (2003), 167(2), 130-136

Rationale: In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol. Objectives: The present ... [more ▼]

Rationale: In spite of many recent studies on the effects of acetaldehyde, it is still unclear whether acetaldehyde mediates the reinforcing and/or aversive effects of ethanol. Objectives: The present study reexamined the role of acetaldehyde in ethanol-induced conditioned taste aversion (CTA). A first experiment compared ethanol- and acetaldehyde-induced CTA. In a second experiment, cyanamide, an aldehyde dehydrogenase inhibitor, was administered before conditioning with either ethanol or acetaldehyde to investigate the effects of acetaldehyde accumulation. Methods: A classic CTA protocol was used to associate the taste of a saccharin solution with either ethanol or acetaldehyde injections. In experiment 1, saccharin consumption was followed by injections of either ethanol (0, 0.5, 1.0, 1.5 or 2.0 g/kg) or acetaldehyde (0, 100, 170 or 300 mg/kg). In experiment 2, the rats were pretreated with either saline or cyanamide (25 mg/kg) before conditioning with either ethanol or acetaldehyde. Results: Both ethanol and acetaldehyde induced significant CTA. However, ethanol produced a very strong CTA relative to acetaldehyde that induced only a weak CTA even at toxic doses. Cyanamide pretreatments significantly potentiated ethanol- but not acetaldehyde-induced CTA. Conclusions: The present results indicate that ethanol-induced CTA does not result from brain acetaldehyde effects. In contrast, it is suggested that the reinforcing effects of brain acetaldehyde might actually reduce ethanol-induced CTA. Our results also suggest that the inhibition of brain catalase activity may contribute to the potentiating effects of cyanamide on ethanol-induced CTA. [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 detailShort-term contextual sensitisation and conditioned hyperkinesia produced by cocaine in suckling rats aged 4-10 days and 14-20 days
Tirelli, Ezio ULg

in Psychopharmacology (2001), 156(1), 46-52

RATIONALE: It was hypothesised that the failure to generate sensitisation to the behavioural effects of a motor stimulant in suckling rats was mainly due to not pairing the drug with the test context ... [more ▼]

RATIONALE: It was hypothesised that the failure to generate sensitisation to the behavioural effects of a motor stimulant in suckling rats was mainly due to not pairing the drug with the test context during chronic pretreatment. OBJECTIVE: This study probed the capabilities of neonatal and infant rat pups to show short-term context-specific sensitisation and conditioned drug activity produced by cocaine. METHODS: Two similar experiments were conducted on rat pups aged 4-10 days or 14-20 days, each experiment comprising three phases: a sensitisation phase (days 4-8 and days 14-18 of age), a test session under cocaine for context specificity of sensitisation (day 9 and day 19 of age) and a test session under saline for conditioned drug effects (day 10 and day 20 of age). Over five daily sessions, pups first received an injection of either 16 mg/kg cocaine (paired group) or saline (unpaired group) in test chambers, and 110 min later the converse injections in the vivarium (in a cage that was different from the home cage). A third group received saline in both contexts. Behaviour was scored using videotapes. RESULTS: Sensitisation developed in the paired groups at both ages. In 4- to 10-day-old pups, sensitisation was expressed via locomotion (matrix crosses) and also horizontal and vertical activities (categories comprising several age-specific movements). In 14- to 18-day-old pups, it was displayed by increases in head movements and vertical activity, and by a decline in stationary position. These effects were confirmed to be context specific on the test sessions (day 9 or day 19), the paired groups producing by far the greatest values. On the conditioning test, the paired groups also produced the greatest amounts of the above-mentioned behaviours, revealing a conditioned drug effect. Additionally, the conditioned effect scores were higher than those of two additional groups that had been treated similarly to the others but outside the chamber until the two tests (controlling for a withdrawal effect and possible novelty-induced activity in the test context). There were no differences between these unexposed groups, indicating that no abstinence effect occurred. CONCLUSIONS: The results demonstrate that neonatal rats are capable of showing physiological/non-contextual cocaine-induced behavioural sensitisation as well as its context-specific expression and the conditioned activity following its establishment. [less ▲]

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See detailThe behavioral effects of acute and chronic JL 13, a putative antipsychotic, in Cebus non-human primates
Casey, Daniel; Bruhwyler, Jacques; Delarge, Jacques et al

in Psychopharmacology (2001), 157

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See detailSelective effects of nicotine on attentional processes
Mancuso, G.; Warburton, D. M.; Melen, Marie-Rose ULg et al

in Psychopharmacology (1999), 146(2), 199-204

RATIONALE: It is now well established from electrophysiological and behavioural evidence that nicotine has effects on information processing. The results are usually explained either by a primary effect ... [more ▼]

RATIONALE: It is now well established from electrophysiological and behavioural evidence that nicotine has effects on information processing. The results are usually explained either by a primary effect of nicotine or by a reversal effect of a nicotine-induced, abstinence deficit. In addition, there is dispute about the cognitive processes underlying the changes in performance. METHODS: This study has approached the first question by using the nicotine patch, in order to administer nicotine chronically. In addition, we examined the effects of nicotine on attention with a selection of tests which assessed the intensity and selectivity features of attention, using the Random Letter Generation test, the Flexibility of Attention test and the Stroop test. RESULTS: Nicotine enhanced the speed of number generation and the speed of processing in both the control and interference conditions of the Stroop test. There were no effects on attentional switching of the Flexibility of Attention test. CONCLUSION: The results are consistent with the hypothesis that nicotine mainly improves the intensity feature of attention, rather than the selectivity feature. [less ▲]

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See detailEffects on nicotine administered via a transdermal delivery system on vigilance : a repeated measure study
Mancuso, Giovanna; Andrès Bénito, Pilar; Ansseau, Marc ULg et al

in Psychopharmacology (1999), 142(1), 18-23

Tested 15 male smokers (aged 18-25 yrs) in a within-Ss design to determine the influence of a transdermal patch of 21 mg nicotine on vigilance. Ss were tested on the Rapid Visual Information Processing ... [more ▼]

Tested 15 male smokers (aged 18-25 yrs) in a within-Ss design to determine the influence of a transdermal patch of 21 mg nicotine on vigilance. Ss were tested on the Rapid Visual Information Processing test 1.3, 3 and 6.3 hrs after patch application, to verify the involvement of the dose of nicotine on the performance. The results confirm and extend the knowledge on the increasing effects of nicotine on vigilance previously found with orally and transdermally administered nicotine. Moreover, results show that such performance was independent of the time of nicotine absorption, which suggests that a relatively low dose of nicotine suffices to activate vigilance processing. Regarding motor performance, no convincing effect of nicotine was observed on reaction time. ((c) 1999 APA/PsycINFO, all rights reserved) [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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See detailVerticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice
Tirelli, Ezio ULg; Witkin, J. M.

in Psychopharmacology (1994), 116(2), 191-200

Behavioral effects of dopaminergic stimulation were compared for C57BL/6J mice and DBA/2J mice. Effects of apomorphine (APO) alone and in combination with cocaine (COC) were assessed using a time-sampling ... [more ▼]

Behavioral effects of dopaminergic stimulation were compared for C57BL/6J mice and DBA/2J mice. Effects of apomorphine (APO) alone and in combination with cocaine (COC) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Climbing occurred in DBA/2J mice only at doses of APO that were 16 times higher than the smallest effective dose in C57BL/6J mice, but relative to baseline values, effects were comparable. Whereas DBA/2J mice showed dose-dependent leaning under APO, C57BL/6J mice exhibited significantly increased leaning only after the highest APO dose. When given alone, COC produced significant climbing, but not leaning or gnawing, in either strain. COC potentiated APO-induced climbing and gnawing in both strains but did not consistently change APO-induced leaning in either strain. APO alone reduced locomotor activity and attenuated COC-induced hyperkinesia. ((c) 1997 APA/PsycINFO, all rights reserved) [less ▲]

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See detailBiphasic locomotor effects of the dopamine D-sub-1 agonist SKF 38393 and their attenuation in non-habituated mice
Tirelli, Ezio ULg; Terry, P.

in Psychopharmacology (1993), 110(1-2), 69-75

Examined the locomotor stimulatory effects of the dopamine D-sub-1 receptor partial agonist SKF 38393 in male C57B1/6J mice. Non-habituated mice showed marked dose-related (3-300 mg/kg, subcutaneously ... [more ▼]

Examined the locomotor stimulatory effects of the dopamine D-sub-1 receptor partial agonist SKF 38393 in male C57B1/6J mice. Non-habituated mice showed marked dose-related (3-300 mg/kg, subcutaneously) locomotor stimulation. The time-course effect was biphasic at very high doses (100-300 mg/kg), with dose-related locomotor depression followed by dose-related long-term hyperlocomotion. For all doses, locomotor effects were detectable throughout the 4-hr test period. To determine whether these effects were mediated by D-sub-1 receptor stimulation, effects of SKF 38393 were assessed in combination with behaviorally inactive and active doses (0.1 and 0.2 mg/kg, respectively) of the selective D-sub-1 receptor antagonist SCH 39166. Both doses of SCH 39166 attenuated the hyperlocomotion induced by 30 mg/kg of the agonist to a similar degree. However, neither dose was able to reverse either the depressant or the stimulatory effects of 300 mg/kg SKF 38393. ((c) 1997 APA/PsycINFO, all rights reserved) [less ▲]

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