Modulation of the locomotor responses induced by D1-like and D2-like dopamine receptor agonists and D-amphetamine by NMDA and non-NMDA glutamate receptor agonists and antagonists in the core of the rat nucleus accumbens.

Dopamine and glutamate interactions in the nucleus accumbens (NAcc) play a crucial role in both the development of a motor response suitable for the environment and in the mechanisms underlying the motor-activating properties of psychostimulant drugs such as amphetamine. We investigated the effects of the infusion in the NAcc of NMDA and non-NMDA receptor agonists and antagonists on the locomotor responses induced by the selective D(1)-like receptor agonist SKF 38393, the selective D(2)-like receptor agonist quinpirole, alone or in combination, and D-amphetamine. Infusion of either the NMDA receptor agonist NMDA, the NMDA receptor antagonist D-AP5, the non-NMDA receptor antagonist CNQX, or the non-NMDA receptor agonist AMPA resulted in an increase in basal motor activity.

Resting-state brain glucose utilization as measured by PET is directly related to regional synaptophysin levels: a study in baboons.

It is classically recognized that regional cerebral glucose consumption (CMRglc), as measured by positron emission tomography (PET) and [18F]-2-fluorodeoxyglucose (FDG), is a precise index of the integrated local neuronal activity. However, despite extensive use of the FDG-PET method, the significance of the measured CMRglc has been little addressed so far. In the present study, we aimed for the first time to test whether resting-state CMRglc is directly related to synaptic density.

Transforming growth factor-beta and ischemic brain injury.

1. Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by using the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man.

[Does transforming growth factor-beta (TGF-beta) act as a neuroprotective agent in cerebral ischemia?].

Necrosis and apoptosis are the two fundamental hallmarks of neuronal death in stroke. Nevertheless, thrombolysis, by means of the recombinant serine protease t-PA, remains until now the only approved treatment of stroke in man. Over the last years, the cytokine termed Transforming Growth Factor-beta 1 (TGF-beta 1) has been found to be strongly up regulated in the central nervous system following ischemia-induced brain damage.

Synthesis and biological evaluation of halogenated naphthyridone carboxamides as potential ligands for in vivo imaging studies of substance P receptors.

With the aim of developing new radioligands for in vivo studies of substance P receptors using positron emission tomography or single photon emission computed tomography, 2- and 3-halo naphthyridone-6-carboxamide derivatives were synthesized. Their affinities toward the target receptors were evaluated on CHO cells and compared to the unsubstituted analogue EP 00652218 (IC(50) = 100 nM +/- 20). The IC(50) value was not altered in the case of 2-chloro compound 1 (IC(50) = 100 nM +/- 15) and only slightly reduced for the 2-fluoro and -iodo analogues 6 and 8 (IC(50) = 500 nM +/- 80).

Blockade of the locomotor stimulant effects of amphetamine by group I, group II, and group III metabotropic glutamate receptor ligands in the rat nucleus accumbens: possible interactions with dopamine receptors.

Previous investigations have shown that mGlu receptors would be involved in the amphetamine-induced motor response. However, data are somewhat controversial across studies where methodological protocols vary. The aim of the present study was to determine the involvement of mGlu receptors in the NAcc in the locomotor-activating properties of amphetamine in rats well habituated to their experimental environment, a condition known to modulate the motor response to amphetamine.

Behavioral and neurochemical effects induced by subchronic exposure to 40 ppm toluene in rats.

Chronic toluene inhalation at concentrations above occupational exposure limits (e.g., 100 ppm; NIOSH) has been repeatedly shown to induce neurotoxic effects.

Neural basis of visually guided head movements studied with fMRI.

We used event-related fMRI to measure brain activity while subjects performed saccadic eye, head, and gaze movements to visually presented targets. Two distinct patterns of response were observed. One set of areas was equally active during eye, head, and gaze movements and consisted of the superior and inferior subdivisions of the frontal eye fields, the supplementary eye field, the intraparietal sulcus, the precuneus, area MT in the lateral occipital sulcus and subcortically in basal ganglia, thalamus, and the superior colliculus.

Gamma-aminobutyric acid neuropharmacological investigations on narcosis produced by nitrogen, argon, or nitrous oxide.

Unlabelled: Inhaled anesthetics, including the gaseous anesthetics nitrous oxide and xenon, are thought to act by interacting directly with ion-channel receptors. In contrast, little is known about the mechanism of action of inert gases that show only narcotic potency at high pressures, such as nitrogen or argon. In the present study, we investigated the effects of selective gamma-aminobutyric acid (GABA) receptor antagonists on narcosis produced by nitrogen, argon, and nitrous oxide.

Angiopoietin-1-induced PI3-kinase activation prevents neuronal apoptosis.

Although angiopoietin-1 (Ang-1) is recognized as an endothelial growth factor, its presence in brain following an ischemic event suggests a role in the evolution of neuronal damage. Using primary neuronal cultures, we showed that neurons express Ang-1 and possess the functional angiopoietin-receptor Tie-2, which is phosphorylated in the presence of Ang-1. We further investigated in vitro whether Ang-1 could protect neurons against either excitotoxic necrosis or apoptosis induced by serum deprivation (SD).

Transforming growth factor alpha-induced expression of type 1 plasminogen activator inhibitor in astrocytes rescues neurons from excitotoxicity.

Although transforming growth factor (TGF)-alpha, a member of the epidermal growth factor (EGF) family, has been shown to protect neurons against excitotoxic and ischemic brain injuries, its mechanism of action remains unknown. In the present study, we used in vitro models of apoptotic or necrotic paradigms demonstrating that TGF-alpha rescues neurons from N-methyl-D-aspartate (NMDA)-induced excitotoxic death, with the obligatory presence of astrocytes. Because neuronal tissue-type plasminogen activator (t-PA) release was shown to potentiate NMDA-induced excitotoxicity, we observed that TGF-alpha treatment reduced NMDA-induced increase of t-PA activity in mixed cultures of neurons and astrocytes.

The neural basis of intrusions in free recall and cued recall: a PET study in Alzheimer's disease.

This study was designed to map in Alzheimer's disease patients the correlations between resting-state brain glucose utilization measured by PET and the number of intrusions obtained by means of a specially designed episodic memory test separately in free recall and in cued recall. SPM revealed significant negative correlations between the number of intrusions in free recall and the metabolism of the right superior frontal gyrus. For the intrusions in cued recall, the negative correlations concerned the left rhinal cortex.

The metabolic substrates of bradykinesia and tremor in uncomplicated Parkinson's disease.

The pathophysiological mechanisms of bradykinesia and resting tremor, i.e., two major features of Parkinson's disease (PD), remain incompletely understood despite extensive studies, including functional imaging investigations.

Transient global amnesia: concomitant episodic memory and positron emission tomography assessment in two additional patients.

Transient global amnesia (TGA) is characterized by a profound but transient deficit of episodic memory. The study of cerebral blood flow and oxygen metabolism with positron emission tomography (PET) provides relevant pathophysiologic data, but only three patients have been reported so far and in only one was concomitant neuropsychological testing performed. We report here the concomitant neuropsychological and PET assessment of two additional patients.

Excitotoxic lesions of the rhinal cortex in the baboon differentially affect visual recognition memory, habit memory and spatial executive functions.

To specify the functional role of the rhinal cortex, baboons with bilateral excitotoxic lesions of the rhinal cortex (RH group) were tested on a series of computerized memory and learning tasks. Preoperatively, they were trained to and then tested on a delayed nonmatching-to-sample (DNMS) task with trial-unique stimuli. Postoperatively, this visual recognition memory task was given twice.

The neural substrates of episodic memory impairment in Alzheimer's disease as revealed by FDG-PET: relationship to degree of deterioration.

In a previous investigation, we raised the hypothesis that in Alzheimer's disease the cerebral structures implicated in episodic memory deficits may differ according to the severity of cognitive impairment. To test this hypothesis, Story Recall test scores and PET measurements of resting cerebral glucose utilization, a measure of synaptic integrity, were obtained in 40 patients. Using SPM96 (statistical parametric mapping 1996), positive correlations between the two sets of data were calculated on a voxel basis, first in the whole patient sample and then separately in the two subgroups of 20 patients differing in Mini-Mental State Examination score, i.

Group III metabotropic glutamate receptors and D1-like and D2-like dopamine receptors interact in the rat nucleus accumbens to influence locomotor activity.

Evidence for functional interactions between metabotropic glutamate (mGlu) receptors and dopamine (DA) neurotransmission is now clearly established. In the present study, we investigated interactions between group III mGlu receptors and D1- and D2-like receptors in the nucleus accumbens (NAcc). Administration, into the NAcc, of the selective group III mGlu receptor agonist, AP4, resulted in an increase in locomotor activity, which was blocked by pretreatment with the group III mGlu receptor antagonist, MPPG.

[Eye tracking disorders in schizophrenic patients and their parents].

Unlabelled: Several studies have confirmed the existence of genetic factors in schizophrenia. However, the genotype predisposing for the disease is not known yet. Nevertheless, those genetic factors in the families of schizophrenic patients urge us to search for genetic vulnerability markers of schizophrenia.

Executive/attentional cognitive functions in schizophrenic patients and their parents: a preliminary study.

The aim of this study was to determine whether executive/attentional cognitive performances could be considered as markers of vulnerability to schizophrenia. The Stroop Color Word and fluency tests were significantly impaired in schizophrenic patients and their parents compared to controls matched on age and sex while performances on Nelson's Modified Card Sorting Test and the Trail Making Test did not differ. The impairments on the Stroop and fluency could be considered as endophenotypic markers of schizophrenia.

A soluble transforming growth factor-beta (TGF-beta ) type I receptor mimics TGF-beta responses.

Transforming growth factor-beta (TGF-beta) signaling requires a ligand-dependent interaction of TGF-beta receptors Tau beta R-I and Tau beta R-II. It has been previously demonstrated that a soluble TGF-beta type II receptor could be used as a TGF-beta antagonist. Here we have generated and investigated the biochemical and signaling properties of a soluble TGF-beta type I receptor (Tau beta RIs-Fc).

Differential modulation of the D1-like- and D2-like dopamine receptor-induced locomotor responses by group II metabotropic glutamate receptors in the rat nucleus accumbens.

There is strong evidence for the existence of functional interactions between metabotropic glutamate receptors and dopamine transmission in the nucleus accumbens. In the present study, we investigated the interactions between group II mGlu receptors and D1-like- and D2-like receptors in the rat nucleus accumbens. Administration of the selective group II metabotropic glutamate receptor agonist APDC, which had no effect when injected alone, potentiated the locomotor response produced by the selective D1-like receptor agonist SKF 38393 but had no effect on those induced by the selective D2-like receptor agonist quinpirole (also known as LY 171555)--a compound believed to act only at D2-like presynaptic receptors when injected alone--or co-administration of SKF 38393+quinpirole--a pharmacological condition thought to stimulate both D1-like receptors and presynaptic and postsynaptic D2-like receptors.

Inhibition of the glutamate transporter by L-trans-PDC in the nucleus accumbens prevents the locomotor response to amphetamine.

Infusion in the nucleus accumbens of the glutamate uptake inhibitor L-trans-PDC prevented the amphetamine-induced locomotor response. Since L-trans-PDC has been shown to block the amphetamine-induced increase in glutamate but not in DA release, our result indicates that the glutamate transporter is an obligatory target for the activating properties of amphetamine.

The group I metabotropic glutamate receptor antagonist S-4-CPG modulates the locomotor response produced by the activation of D1-like, but not D2-like, dopamine receptors in the rat nucleus accumbens.

Functional interactions between dopamine (DA) and glutamate neurotransmissions in both the dorsal and the ventral striatum have been described for long time. However, there is much controversy as to whether glutamate transmission stimulates or attenuates DA release and locomotor activity. We investigated the functional interactions on locomotor activity between group I metabotropic glutamatergic receptors (mGlu receptors) and both D1-like and D2-like DA receptors in the rat nucleus accumbens.

Contributions of frontal and medial temporal regions to verbal episodic memory: a PET study.

Using PET, subtraction and correlation analysis were jointly employed to determine the specific and complementary contributions of frontal and medial temporal regions to verbal episodic encoding and retrieval processes. Subtraction analysis highlighted prefrontal rCBF increases which were predominantly left-sided during intentional encoding and exclusively right-sided during retrieval, the latter being moreover associated with bilateral precuneus activation. However, significant correlation between rCBF values obtained during intentional encoding and performance scores obtained during retrieval concerned, among other regions, the left parahippocampal gyrus, which indicated that the higher the neuronal activity in this medial temporal region during encoding, the better the retrieval performance.

The use of cerebral blood flow as an index of neuronal activity in functional neuroimaging: experimental and pathophysiological considerations.

Over recent years, activation studies that have been undertaken using brain imaging techniques, such as functional magnetic resonance imaging, positron emission tomography or near infrared spectroscopy, have greatly improved our knowledge of the functional anatomy of the brain. Nevertheless, activation studies do not directly quantify the variations of synaptic transmission (neuronal activity) but detect it indirectly either through the visualisation of changes in cerebral blood flow, oxidative or glycolytic metabolism (for positron emission tomography), or through the measurement of a global index that is dependent on both cerebral blood flow and oxidative metabolism (for functional magnetic resonance imaging and near infrared spectroscopy). Such approaches are based on the concept of a tight parallelism--termed coupling--between variations in neuronal activity, metabolism and cerebral blood flow.