Bernard Le Foll - Academia.edu (original) (raw)

Papers by Bernard Le Foll

Reviews, 2016

Cannabis use disorder is the most commonly reported illegal substance use disorder in the general... more Cannabis use disorder is the most commonly reported illegal substance use disorder in the general population; although demand for assistance from health services is increasing internationally, only a minority of those with the disorder seek professional assistance. Treatment studies have been published, but pressure to establish public policy requires an updated systematic review of cannabis-specific treatments for adults. To evaluate the efficacy of psychosocial interventions for cannabis use disorder (compared with inactive control and/or alternative treatment) delivered to adults in an out-patient or community setting. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 6), MEDLINE, EMBASE, PsycINFO, the Cumulaive Index to Nursing and Allied Health Literature (CINAHL) and reference lists of articles. Searched literature included all articles published before July 2015. All randomised controlled studies examining a psychosocial intervention for cannabis use disorder (without pharmacological intervention) in comparison with a minimal or inactive treatment control or alternative combinations of psychosocial interventions. We used standard methodological procedures as expected by The Cochrane Collaboration. We included 23 randomised controlled trials involving 4045 participants. A total of 15 studies took place in the United States, two in Australia, two in Germany and one each in Switzerland, Canada, Brazil and Ireland. Investigators delivered treatments over approximately seven sessions (range, one to 14) for approximately 12 weeks (range, one to 56).Overall, risk of bias across studies was moderate, that is, no trial was at high risk of selection bias, attrition bias or reporting bias. Further, trials included a large total number of participants, and each trial ensured the fidelity of treatments provided. In contrast, because of the nature of the interventions provided, participant blinding was not possible, and reports of researcher blinding often were unclear or were not provided. Half of the reviewed studies included collateral verification or urinalysis to confirm self report data, leading to concern about performance and detection bias. Finally, concerns of other bias were based on relatively consistent lack of assessment of non-cannabis substance use or use of additional treatments before or during the trial period.A subset of studies provided sufficient detail for comparison of effects of any intervention versus inactive control on primary outcomes of interest at early follow-up (median, four months). Results showed moderate-quality evidence that approximately seven out of 10 intervention participants completed treatment as intended (effect size (ES) 0.71, 95% confidence interval (CI) 0.63 to 0.78, 11 studies, 1424 participants), and that those receiving psychosocial intervention used cannabis on fewer days compared with those given inactive control (mean difference (MD) 5.67, 95% CI 3.08 to 8.26, six studies, 1144 participants). In addition, low-quality evidence revealed that those receiving intervention were more likely to report point-prevalence abstinence (risk ratio (RR) 2.55, 95% CI 1.34 to 4.83, six studies, 1166 participants) and reported fewer symptoms of dependence (standardised mean difference (SMD) 4.15, 95% CI 1.67 to 6.63, four studies, 889 participants) and cannabis-related problems compared with those given inactive control (SMD 3.34, 95% CI 1.26 to 5.42, six studies, 2202 participants). Finally, very low-quality evidence indicated that those receiving intervention reported using fewer joints per day compared with those given inactive control (SMD 3.55, 95% CI 2.51 to 4.59, eight studies, 1600 participants). Notably, subgroup analyses found that interventions of more than four sessions delivered over longer than one month (high intensity) produced consistently improved outcomes (particularly in terms of cannabis use frequency and severity of dependence) in the short term as compared with low-intensity interventions.The most consistent evidence supports the use of cognitive-behavioural therapy (CBT), motivational enhancement therapy (MET) and particularly their combination for assisting with reduction of cannabis use frequency at early follow-up (MET: MD 4.45, 95% CI 1.90 to 7.00, four studies, 612 participants; CBT: MD 10.94, 95% CI 7.44 to 14.44, one study, 134 participants; MET + CBT: MD 7.38, 95% CI 3.18 to 11.57, three studies, 398 participants) and severity of dependence (MET: SMD 4.07, 95% CI 1.97 to 6.17, two studies, 316 participants; MET + CBT: SMD 7.89, 95% CI 0.93 to 14.85, three studies, 573 participants), although no particular intervention was consistently effective at nine-month follow-up or later. In addition, data from five out of six studies supported the utility of adding voucher-based incentives for cannabis-negative urines to enhance treatment effect on cannabis use frequency. A single study found contrasting results throughout…

The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP), Jan 4, 2016

Multiple studies suggest a pivotal role of the endocannabinoid system in regulating the reinforci... more Multiple studies suggest a pivotal role of the endocannabinoid system in regulating the reinforcing effects of various substances of abuse. Rimonabant, a CB1 inverse agonist found to be effective for smoking cessation, was associated with an increased risk of anxiety and depression. Here we evaluated the effects of the CB1 neutral antagonist AM4113 on the abuse-related effects of nicotine and its effects on anxiety and depressive-like behavior in rats. Rats were trained to self-administer nicotine under a fixed-ratio 5 or progressive-ratio schedules of reinforcement. A control group was trained to self-administer food. The acute/chronic effects of AM4113 pretreatment were evaluated on nicotine taking, motivation for nicotine and cue-, nicotine primingand yohimbine-induced reinstatement of nicotine-seeking. The effects of AM4113 in the basal firing and bursting activity of midbrain dopamine neurons were evaluated in a separate group of animals treated with nicotine. Anxiety/depressio...

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014

Tobacco produces an impressive burden of disease resulting in premature death in half of users. D... more Tobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A 'bench to bedside strategy' was initially used to develop cannabinoid CB 1 receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A 'bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence.

Behavioural Brain Research, 2015

Our prior work demonstrated the involvement of the caudal granular subregion of the insular corte... more Our prior work demonstrated the involvement of the caudal granular subregion of the insular cortex in a rat model of nicotine self-administration. Recent studies in various animal models of addiction for nicotine and other drugs have identified a role for the rostral agranular subregion (RAIC). The current research was undertaken to examine the involvement of the RAIC in a rat model of nicotine self-administration. We investigated the inactivating effects of local infusions of a γ-aminobutyric acid agonist mixture (baclofen/muscimol) into the RAIC on nicotine self-administration under a fixed-ratio 5 (FR-5) schedule and on reinstatement of nicotine seeking induced by nicotine-associated cues in rats. We also evaluated the effects of RAIC inactivation on food self-administration under an FR5 schedule as a control. Inactivation of the RAIC decreased nicotine, but not food, self-administration. RAIC inactivation also prevented the reinstatement, after extinction, of nicotine seeking induced by nicotine-associated cues. Our study indicates that the RAIC is involved in nicotine-taking and nicotine-seeking in rats. Modulating insular cortex function appears to be a promising approach for nicotine dependence treatment.

Canadian journal of public health = Revue canadienne de santé publique

ABSTRACT No abstract available.

Neuropsychopharmacology, 2015

Substance-related and addictive disorders, particularly gambling disorder, are known to be associ... more Substance-related and addictive disorders, particularly gambling disorder, are known to be associated with risky decision-making behavior. Several neuroimaging studies have identified the involvement of the insular cortex in decision making under risk. However, the extent of this involvement remains unclear and the specific contributions of two distinct insular subregions, the rostral agranular (RAIC) and the caudal granular (CGIC), have yet to be examined. Rats were trained to perform a rodent gambling task (rGT), in which subjects chose between four options that differed in the magnitude and probability of rewards and penalties. In order to address the roles of the RAIC and CGIC in established choice behavior, pharmacological inactivations of these two subregions via local infusions of GABA receptor agonists, were performed following 30 rGT training sessions. The contribution made by the RAIC or CGIC to the acquisition of choice behavior was also determined by lesioning these areas prior to behavioral training. Inactivation of the RAIC, but not of the CGIC, shifted rats&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; preference towards options with greater reward frequency and lower punishment. Prior to rGT acquisition, lesions of the RAIC, but not the CGIC, likewise resulted in a higher preference for options with greater reward frequency and lower punishment, and this persisted throughout the 30 training sessions. Our results provide confirmation of the involvement of the RAIC in rGT choice behavior and suggest that the RAIC may mediate detrimental risky decision-making behavior, such as that associated with addiction and gambling disorder.Neuropsychopharmacology accepted article preview online, 08 May 2015. doi:10.1038/npp.2015.133.

Frontiers in psychiatry, 2015

Several lines of evidence have shown that the endogenous cannabinoids are implicated in several n... more Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction. The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans. Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine's effects. Those recent findings suggest possible alternative ways o...

Emerging evidence indicates that the DRD1-BDNF-DRD3 cluster plays an important role in nicotine a... more Emerging evidence indicates that the DRD1-BDNF-DRD3 cluster plays an important role in nicotine addiction. We have performed an association analysis of 42 SNPs within these genes with cigarette consumption in a group of 341 schizophrenia patients. The ACCG haplotype consisting of four BDNF markers (Val66Met (rs6265), rs11030104, rs2049045 and rs7103411) showed an association with the risk of smoking (p = 0.0002). Both DRD1 markers tested (rs4532 and rs686) and the DRD3 marker (rs1025398) showed association with quantity of tobacco smoked (p = 0.01, 0.005 and 0.002, respectively). Our findings are preliminary; however, they support the involvement of the DRD1, BDNF and DRD3 genes in smoking behaviour.

Hedonic and reinforcing properties of drugs of abuse are closely related to brain dopamine neuron... more Hedonic and reinforcing properties of drugs of abuse are closely related to brain dopamine neuron activity. All these drugs increase dopamine release in the shell of nucleus accumbens, a brain region in which neurons co-express the D 1 (DIR) and D 3 (D3R) dopamine receptor subtypes, that converging pharmacological, human post-mortem and genetic studies suggest to be implicated in drug addiction. The D3R, through a cross-talk with the DIR, is involved in induction and expression of behavioral sensitization to levodopa in rats bearing unilateral lesions of dopamine neurons. Behavioral sensitization, a cardinal feature of addiction arises from repeated administration of drugs of abuse is thought to play a role in intensification of reinforcing efficacy of these drugs observed under certain conditions. Stimulation of the D3R also appears to enhance the reinforcing effect of cocaine in rats. By interacting with these processes, D3R agents have potential therapeutic applications for treating drug addiction. BP 897 (N-[4-(4-(2-methoxyphenyl) piperazin-l-yl) butyl] naphtalen 2-carboxamide dichlorhydrate), a partial and highly selective D3R agonist in vitro, behaves as an agonist or an antagonist in vivo depending on the response considered. BP 897 has the unprecedented property to reduce cocaine-seeking behavior induced by presentation of a cocaine-associated cue, without having any intrinsic reinforcing effect. As drug-associated cues maintain drug-seeking in animals and elicit craving and relapse in humans, D3R agents like BP 897 may represent new medications for drug addiction, with minimal liability to maintaining dependence.

Frontiers in Pharmacology, 2014

There is considerable interest in developing highly selective dopamine (DA) D3 receptor ligands f... more There is considerable interest in developing highly selective dopamine (DA) D3 receptor ligands for a variety of mental health disorders. DA D3 receptors have been implicated in Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, schizophrenia, anxiety, depression, and substance use disorders. The most concrete evidence suggests a role for the D3 receptor in drug-seeking behaviors. D3 receptors are a subtype of D2 receptors, and traditionally the functional role of these two receptors has been difficult to differentiate. Over the past 10-15 years a number of compounds selective for D3 over D2 receptors have been developed. However, translating these findings into clinical research has been difficult as many of these compounds cannot be used in humans. Therefore, the functional data involving the D3 receptor in drug addiction mostly comes from pre-clinical studies. Recently, with the advent of [(11)C]-(+)-PHNO, it has become possible to image D3 receptors in the human brain with increased selectivity and sensitivity. This is a significant innovation over traditional methods such as [(11)C]-raclopride that cannot differentiate between D2 and D3 receptors. The use of [(11)C]-(+)-PHNO will allow for further delineation of the role of D3 receptors. Here, we review recent evidence that the role of the D3 receptor has functional importance and is distinct from the role of the D2 receptor. We then introduce the utility of analyzing [(11)C]-(+)-PHNO binding by region of interest. This novel methodology can be used in pre-clinical and clinical approaches for the measurement of occupancy of both D3 and D2 receptors. Evidence that [(11)C]-(+)-PHNO can provide insights into the function of D3 receptors in addiction is also presented.

Progress in neuro-psychopharmacology & biological psychiatry, Jan 3, 2014

To improve antipsychotic treatment in schizophrenia patients, many studies have investigated gene... more To improve antipsychotic treatment in schizophrenia patients, many studies have investigated genetic polymorphisms associated with antipsychotic metabolizing enzymes and receptors. While these studies have typically focused on drug response, few have investigated genetic influences on antipsychotic dosage. This study set out to analyze the association between 134 SNPs in 38 candidate genes and antipsychotic dosage in schizophrenia patients. For our analysis, 300 patients with a diagnosis of either schizophrenia or schizoaffective disorder were recruited between the ages of 18 and 75. A cross-sectional assessment was used, in which data were collected from each participant through an interview and self-report questionnaire. Antipsychotic dose was standardized according to the chlorpromazine equivalents, defined daily dose and relative to the maximum dose specified in the product monograph. Participants were genotyped using a Customized Illumina Chip comprising 134 SNPs, and all marke...

The World Journal of Biological Psychiatry, 2014

Objectives. Suicide is a serious public health concern, and it is partly genetic. the brain-deriv... more Objectives. Suicide is a serious public health concern, and it is partly genetic. the brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (dwivedi et al., arch Gen psychiatry 2010;60:804-815; Zai et al., prog neuropsychopharmacol biol psychiatry 2012;34:1412-1418 and bdnF regulates the expression of the dopamine d 3 receptor. Objective. we examined the role of the BDNF and DRD3 genes in suicide. Methods. we analysed four tag single-nucleotide polymorphisms (Snps) in BDNF and 15 Snps in the d 3 receptor gene DRD3 for possible association with suicide attempt history in our Canadian sample of Schizophrenia (SCZ) patients of european ancestry (N  188). Results. in this sample, we found a possible interaction between the BDNF Val66met and DRD3 Ser9Gly Snps in increasing the risk of suicide attempt(s) in our SCZ sample. Specifically, a larger proportion of SCZ patients who were carrying at least one copy of the minor allele at each of the Val66met and Ser9Gly functional markers have attempted suicides compared to patients with other genotypes (bonferroni P  0.05). however, we could not replicate this finding in samples from other psychiatric populations. Conclusions. taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.

Psychopharmacology, 2006

Rationale and background: Tobacco use through cigarette smoking is the leading preventable cause ... more Rationale and background: Tobacco use through cigarette smoking is the leading preventable cause of death in the developed world. Nicotine, a psychoactive component of tobacco, appears to play a major role in tobacco dependence, but reinforcing effects of nicotine often are difficult to demonstrate directly in controlled laboratory studies with animal or human subjects. Objective: To review the major findings obtained with various procedures developed to study dependencerelated behavioral effects of nicotine in experimental animals and humans, i.e., drug self-administration, conditioned place preference, subjective reports of nicotine effects and nicotine discrimination, withdrawal signs, and ratings of drug withdrawal. Results: Nicotine can function as an effective reinforcer of drug-seeking and drug-taking behavior both in experimental animals and humans under appropriate conditions. Interruption of chronic nicotine exposure produces withdrawal symptoms that may contribute to relapse. Difficulties encountered in demonstrating reinforcing effects of nicotine under some conditions, relative to other drugs of abuse, may be due to weaker primary reinforcing effects of nicotine or to a more critical contribution of environmental stimuli to the maintenance of drug-seeking and drug-taking behavior with nicotine than with other drugs of abuse. Further experiments are also needed to delineate the role other chemical substances inhaled along with nicotine in tobacco smoke play in sustaining smoking behavior.

Psychological Medicine, 2014

This book provides a comprehensive and up-to-date overview of the psychiatry and neuroscience of ... more This book provides a comprehensive and up-to-date overview of the psychiatry and neuroscience of Cannabis sativa (marijuana), with particular emphasis on psychotic disorders. It outlines the very latest developments in our understanding of the human cannabinoid system, and links this knowledge to clinical and epidemiological facts about the impact of cannabis on mental health. Clinically focused chapters review not only the direct psychomimetic properties of cannabis, but also the impact consumption has on the courses of evolving or established mental illness such as schizophrenia. A number of controversial issues are critically explored, including whether a discrete 'cannabis psychosis' exists, and whether cannabis can actually cause schizophrenia. Effects of cannabis on mood, notably depression, are reviewed, as are its effects on cognition. This book will be of interest to all members of the mental health team, as well as to neuroscientists and those involved in drug and alcohol research.

Neuropsychopharmacology, 2012

Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It ... more Since cloning of the dopamine receptor D4 (DRD4), its role in the brain has remained unclear. It has been reported that polymorphism of the DRD4 gene in humans is associated with reactivity to cues related to tobacco smoking. However, the role of DRD4 in animal models of nicotine addiction has seldom been explored. In our study, male Long-Evans rats learned to intravenously self-administer nicotine under a fixed-ratio (FR) schedule of reinforcement. Effects of the selective DRD4 antagonist L-745,870 were evaluated on nicotine selfadministration behavior and on reinstatement of extinguished nicotine-seeking behavior induced by nicotine-associated cues or by priming injections of nicotine. L-745,870 was also tested on reinstatement of extinguished food-seeking behavior as a control. In addition, the selective DRD4 agonist PD 168,077 was tested for its ability to reinstate extinguished nicotine-seeking behavior. Finally, L-745,870 was tested in Sprague Dawley rats trained to discriminate administration of 0.4 mg/kg nicotine from vehicle under an FR schedule of food delivery. L-745,870 significantly attenuated reinstatement of nicotine-seeking induced by both nicotine-associated cues and nicotine priming. In contrast, L-745,870 did not affect established nicotine self-administration behavior or reinstatement of foodseeking behavior induced by food cues or food priming. L-745,870 did not produce nicotine-like discriminative-stimulus effects and did not alter discriminative-stimulus effects of nicotine. PD 168,077 did not reinstate extinguished nicotine-seeking behavior. As DRD4 blockade by L-745,870 selectively attenuated both cue-and nicotine-induced reinstatement of nicotine-seeking behavior, without affecting cue-or food-induced reinstatement of food-seeking behavior, DRD4 antagonists are potential therapeutic agents against tobacco smoking relapse.

Neuropsychopharmacology, 2010

Table 2 Response Rates of Rats During the Drug Discrimination Study at Different Nicotine Doses (... more Table 2 Response Rates of Rats During the Drug Discrimination Study at Different Nicotine Doses (0-0.4 mg/kg) After Prazosin (0-1 mg/kg) Pretreatment Nicotine dose (mg/kg) 0 0.01 0.03 0.1 0.3 0.4 Vehicle 2.1 ± 0.3 1.9 ± 0.2 2 ± 0.3 2 ± 0.2 2.2 ± 0.2 2 ± 0.3 Prazosin 0.25 mg/kg 1.8 ± 0.2 1.7 ± 0.3 1.7 ± 0.2 1.9 ± 0.2 2.3 ± 0.2 1.5 ± 0.3 Prazosin 0.5 mg/kg 2±0.2 1.3±0.2 1.7±0.2 1.6±0.2 1.8±0.3 1.7±0.3 Prazosin 1 mg/kg 1.7 ± 0.2 1.7 ± 0.1 2 ± 0.3 1.8 ± 0.2 2 ± 0.2 1.6 ± 0.2 ANOVA F 33,3 ¼ 1.7, NS 1.75, NS 1.95, NS 1.3, NS 1.4, NS 1.3, NS

Journal of Psychopharmacology, 2013

Multiple studies suggest a pivotal role of the endocannabinoid system in the regulation of the re... more Multiple studies suggest a pivotal role of the endocannabinoid system in the regulation of the reinforcing effects of various substances of abuse. Different approaches have been used to modulate endocannabinoid neurotransmission including the use of endogenous cannabinoid anandamide reuptake inhibitors. Previously, the effects of one of them, N-(4-hydroxyphenyl)-arachidonamide (AM404), have been explored in rodents trained to self-administer ethanol and heroin, producing some promising results. Moreover, AM404 attenuated the development and reinstatement of nicotine-induced conditioned place preference (CPP). In this study, we used the nicotine intravenous self-administration procedure to assess the effects of intraperitoneal administration of 0, 1, 3 and 10 mg/kg AM404 on nicotine-taking and food-taking behaviors under fixed-ratio and progressive-ratio schedules of reinforcement, as well as on reinstatement of nicotine-seeking induced by nicotine priming and by presentation of nicotine-associated cues. The ability of AM404 to produce place preference was also evaluated. AM404 did not produce CPP and did not modify nicotine-taking and food-taking behaviors. In contrast, AM404 dose-dependently attenuated reinstatement of nicotine-seeking behavior induced by both nicotine-associated cues and nicotine priming. Our results indicate that AM404 could be a potential promising therapeutic option for the prevention of relapse to nicotine-seeking in abstinent smokers.

Journal of Nuclear Medicine, 2007

The aim of the present study was to explore the applicability of an extracerebral reference regio... more The aim of the present study was to explore the applicability of an extracerebral reference region for the quantification of cerebral receptors with PET. Methods: Male squirrel monkeys underwent quantitative PET studies of cerebral nicotinic acetylcholine receptors (nAChRs) with 2-18 F-fluoro-A-85380 (2-FA). Data from dynamic PET scans were analyzed with various compartmentand non-compartment-based models, including a simplified reference tissue model (SRTM). Nondisplaceable volume-of-distribution (VDnd) values were determined in regions of interest after the blockade of 2-FA-specific binding by nicotine infusion. Binding potential values, estimated with the cerebellum and muscle as reference regions, were compared and the reproducibility of measurements was determined. Results: One-and 2-tissuecompartment modeling and linear graphic analysis provided similar total volume-of-distribution (VD T ) values for each studied region. VD T values were high in the thalamus, intermediate in the cortex and midbrain, and low in the cerebellum and muscle, consistent with the distribution pattern of nAChR containing a 4 and b 2 receptor subunits (a 4 b 2 *). The administration of nicotine at 2 mg/kg/d via an osmotic pump resulted in a nearly complete saturation of 2-FA-specific binding and led to very small changes in volumes of distribution in the cerebellum and muscle (29% 6 4% [mean 6 SEM] and 0% 6 6%, respectively), suggesting limited specific binding of the radioligand in these areas. VD T measured in muscle in 15 monkeys was reasonably constant (3.0 6 0.2, with a coefficient of variation of 8%). VDnd in studied brain regions exceeded VD T in muscles by a factor of 1.3. With this factor and with muscle as a reference region, BP* values calculated for studied brain regions with the SRTM were in good agreement with those obtained with the cerebellum as a reference region. Significant correlations were observed between BP* values estimated with these 2 approaches. The reproducibilities of BP* measurements obtained with the 2 methods were comparable, with coefficients of variation of less than 11% and 13% for the thalamus and the cortex, respectively. Conclusion: These results suggest that the accurate quantification of nAChRs can be performed with 2-FA and a reference region outside the brain, providing a novel approach for the quantification of brain receptors when no suitable cerebral reference region is available.

Journal of Affective Disorders, 2011

Prévalence et facteurs associés des épisodes dépressifs majeurs : Evaluation par la version tunis... more Prévalence et facteurs associés des épisodes dépressifs majeurs : Evaluation par la version tunisienne du CIDI dans les structures de première ligne de Sousse LA TUNISIE MEDICALE -2013 ; Vol 91 (n°04) : 234-239 r é s u m é Prérequis : La dépression majeure représente un trouble mental qui s'accompagne d'un taux de morbidité et de mortalité important. Elle est fréquente en première ligne, mais son épidémiologie, en Tunisie, reste encore peu ou pas connue. But : Déterminer la prévalence et les facteurs associés des épisodes dépressifs majeurs (EDM) dans un échantillon représentatif des consultants dans les structures de première ligne du gouvernorat de Sousse. méthodes : Nous avons procédé à un sondage de deuxième degré et stratifié sur le milieu qui nous a permis de recruter 1246 sujets à interviewer, parmi les consultants de 30 Centres de Santé de Base. Les entretiens ont été réalisés à l'aide du CIDI.2.1., dans une version traduite et validée en dialecte tunisien. Les diagnostics ont été retenus selon les critères de la CIM-10. résultats : L'âge moyen des participants était de 43,4 ± 17,62 ans, avec une prédominance féminine (70,9 %) et urbaine (67,8 %). La prévalence des EDM était de 26,4 %. Elle était associée au sexe féminin, au statut marital de veuf ou divorcé et au milieu rural. Conclusion : La considération de ces facteurs dans l'organisation des soins en première ligne pourrait améliorer le diagnostic et la prise en charge des EDM. Prevalence and correlates of major depressive episodes in Sousse primary care setting: Assessment with Tunisian version of CIDI LA TUNISIE MEDICALE -2013 ; Vol 91 (n°04) : 234-239

European Journal of Neuroscience, 2002

Environmental stimuli previously associated with drug effects can acquire secondary reinforcing p... more Environmental stimuli previously associated with drug effects can acquire secondary reinforcing properties, able to maintain drugseeking behaviour or induce relapse. We have used a classical Pavlovian conditioning procedure to assess the role of the dopamine D 3 receptor (D 3 R) in the expression of drug-conditioned responses. Mice repeatedly receiving cocaine in a particular environment distinct from home-cages displayed hyperlocomotion after subsequent exposure to the drug-paired environment. Cocaine-conditioned hyperactivity was inhibited by BP 897 or SB-277011-A, D 3 R-selective partial agonist and antagonist, respectively. D 3 R gene-targeted mice showed a trend towards an increase in cocaine cue-conditioned hyperactivity. BP 897 had no effect on reactivity to neutral or aversive cues. Cocaine-conditioned mice had increased levels of D 3 R mRNA and binding in the nucleus accumbens (NAc), and transcripts of brain-derived neurotrophic factor (BDNF), a factor controlling D 3 R expression, in the ventral tegmental area (VTA). Cocaine had no effects on D 3 R or BDNF genes when administered in home-cages. Cocaine cue-conditioned c-fos expression was found in cortical areas, notably in the somatosensory cortex, where it was inhibited by BP 897, and in several regions belonging or linked to the limbic system. In conditioned mice, BP 897 inhibited c-fos expression in VTA and activated it in amygdala. These results demonstrate a modulation of reactivity to cocaine cues by the D 3 R, the expression of which is elevated in the NAc by the repeated association of drug effects with a particular context, through a BDNFdependent mechanism. D 3 R-selective partial agonist or antagonist inhibit cocaine cue-conditioned activity possibly by normalizing exacerbated D 3 R function in the NAc, but our results also point to a possible participation of a pathway involving the VTA, amygdala and somatosensory cortex.