Selective antagonism at dopamine D3 receptors attenuates cocaine-seeking behaviour in the rat.

Dopamine (DA) D3 receptors have been suggested to play a role in mechanisms underlying the ability of drug-associated cues to induce drug-seeking behaviour. The present study investigated whether SB-277011-A, a selective DA D3 receptor antagonist, modulates reinstatement of cocaine-seeking behaviour induced by cocaine-associated stimuli. The study also explored whether or not this modulation is generable to seeking behaviours associated with a nutritive reinforcer such as sucrose. Separate groups of rats were trained to associate discriminative stimuli (SD) with the availability of cocaine or sucrose pellets vs. non-reward under a FR1 schedule of reinforcement. Each reinforced response was followed by a response-cue signalling a 20-s time-out (TO). After the self-administration training criterion was met, rats underwent extinction during which cocaine, sucrose pellets and SDs were withheld. Reinstatement tests, separated by 3 d during which rates of responding under extinction conditions remained at the criterion, were performed by presenting SDs non-contingently together with the contingent presentation of response-cues signalling a 20-s TO. Within- and between-subjects experimental designs revealed that 10 and 30 mg/kg SB-277011-A attenuated reinstatement of cocaine-seeking. SB-277011-A (10 mg/kg) did not modify conditioned reinstatement triggered by sucrose pellet-associated cues. These results, provided they can be extrapolated to abstinent human addicts, suggest the potential therapeutic use of selective DA D3 receptor antagonists for the prevention of cue-controlled cocaine-seeking and relapse

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots

This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts

Single-particle tracking uncovers dynamics of glutamate-induced retrograde transport of NF-κB p65 in living neurons

Retrograde transport of NF-κB from the synapse to the nucleus in neurons is mediated by the dynein/dynactin motor complex and can be triggered by synaptic activation. The calibre of axons is highly variable ranging down to 100 nm, aggravating the investigation of transport processes in neurites of living neurons using conventional light microscopy. In this study we quantified for the first time the transport of the NF-κB subunit p65 using high-density single-particle tracking in combination with photoactivatable fluorescent proteins in living mouse hippocampal neurons. We detected an increase of the mean diffusion coefficient (Dmean) in neurites from 0.12 ± 0.05 µm2/s to 0.61 ± 0.03 µm2/s after stimulation with glutamate. We further observed that the relative amount of retrogradely transported p65 molecules is increased after stimulation. Glutamate treatment resulted in an increase of the mean retrograde velocity from 10.9 ± 1.9 to 15 ± 4.9 µm/s, whereas a velocity increase from 9 ± 1.3 to 14 ± 3 µm/s was observed for anterogradely transported p65. This study demonstrates for the first time that glutamate stimulation leads to an increased mobility of single NF-κB p65 molecules in neurites of living hippocampal neurons

Adult Palatum as a Novel Source of Neural Crest-Related Stem Cells

Somatic neural and neural crest stem cells are promising sources for cellular therapy of several neurodegenerative diseases. However, because of practical considerations such as inadequate accessibility of the source material, the application of neural crest stem cells is strictly limited. The secondary palate is a highly regenerative and heavily innervated tissue, which develops embryonically under direct contribution of neural crest cells. Here, we describe for the first time the presence of nestin-positive neural crest-related stem cells within Meissner corpuscles and Merkel cell-neurite complexes located in the hard palate of adult Wistar rats. After isolation, palatal neural crest-related stem cells (pNC-SCs) were cultivated in the presence of epidermal growth factor and fibroblast growth factor under serum-free conditions, resulting in large amounts of neurospheres. We used immunocytochemical techniques and reverse transcriptase-polymerase chain reaction to assess the expression profile of pNC-SCs. In addition to the expression of neural crest stem cell markers such as Nestin, Sox2, and p75, we detected the expression of Klf4, Oct4, and c-Myc. pNC-SCs differentiated efficiently into neuronal and glial cells. Finally, we investigated the potential expression of stemness markers within the human palate. We identified expression of stem cell markers nestin and CD133 and the transcription factors needed for reprogramming of somatic cells into pluripotent cells: Sox2, Oct4, Klf4, and c-Myc. These data show that cells isolated from palatal rugae form neurospheres, are highly plastic, and express neural crest stem cell markers. In addition, pNC-SCs may have the ability to differentiate into functional neurons and glial cells, serving as a starting point for therapeutic studies. Stem Cells 2009;27:1899–191

Rôle de la cholecystokinine, de la neurotensine et des opioides endogènes dans la modulation de la stimulation électrique renforcante du faisceau télencéphalique médian chez le rat

Doctorat en Psychologie -- UCL, 199

Utilisation du conditionnement discriminatif en pharmacologie comportementale

Summary : Drug Discrimination in behavioral pharmacology. Behavioral pharmacology has evolved into an interdisciplinary research trying to qualify and to quantify the pharmacological effects of drugs using behavioral procedures. Most commonly, animals are trained to learn a drug vs. no drug discrimination in a two lever operant task and rely on cues provided by the drug to make the distinction. The so-called Drug Discrimination Paradigm allows to study dose-effect curves, behavioral and pharma-cological drug actions and the classification of new compounds among existing drug categories. By pressing the drug lever animals are reinforced after drug administration ; by pressing the vehicle lever they are reinforced after vehicle injection. When discrimination conditioning has been esta-blished between the drug and the non drug condition, tests with other dosages and other drugs can be run allowing thus to classify drugs without studying their direct effects on behavior. Key words : behavioral pharmacology, drug discrimination paradigm, stimulus properties of drugs.Résumé La pharmacologie comportementale dont l'objectif principal est d'étudier les effets des drogues sur le comportement, fait du paradigme de la discrimination un outil de recherche fondamental très complexe dont les conditions expérimentales sont aiséments comparables. D'une manière générale, des animaux placés dans une cage opérante à deux leviers apprennent à discriminer une drogue d'une solution saline. Chaque type d'injection nécessite de la part du sujet l'appui d'un levier déterminé. Une relation s'instaure progressivement entre les stimuli pharmacologiques et les réponses comportementales. Les tests de généralisation permettent de déterminer la variation possible de la réponse discriminative, face à la présentation de nouveaux stimuli. Mots clés : pharmacologie comportementale, discrimination, drogues.Gewiss Muriel, Heidbreder Christian, De Witte Philippe. Utilisation du conditionnement discriminatif en pharmacologie comportementale. In: L'année psychologique. 1989 vol. 89, n°3. pp. 411-428