A reduced extracellular serotonin level increases the 5-HT1A PET ligand 18F-MPPF binding in the rat hippocampus.

Unlabelled: 4,2'-(Methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine ((18)F-MPPF) is a radiotracer used in clinical PET studies for the visualization of serotonin-1A (5-HT(1A)) receptors. In a previous study, we demonstrated that a rapid enhancement of extracellular serotonin concentrations influences (18)F-MPPF-specific binding. Because endogenous serotonin is significantly decreased in some pathologies, the aim of this study was to determine whether (18)F-MPPF is sensitive to depletion of this neurotransmitter.

Carbon-11 labelling of 8[[3-[4-(2-[(11)C]methoxyphenyl)piperazin-1-yl]-2-hydroxypropyl]oxy]thiochroman, a presynaptic 5-HT(1A) receptor agonist, and its in vivo evaluation in anaesthetised rat and in awake cat.

A new compound, 8[[3-[4-(2-[(11)C]methoxyphenyl)piperazin-1-yl]-2-hydroxypropyl]oxy]thiochroman was labeled via O-methylation with [(11)C]methyl iodide in good yield and specific activity. Original biological evaluations included (i) the study in anesthetized rat with a beta-sensitive intracerebral probe (beta-Microprobe), allowing to measure locally the kinetic of the new PET ligand, and (ii) a PET-scan on a conditioned cat maintained awake during the acquisition. In both in vivo techniques, the new ligand did not reveal any specific binding in hippocampus indicating that this radiotracer is not suitable for mapping 5HT(1A) receptors using positron emission tomography.

Displacement of the PET ligand 18F-MPPF by the electrically evoked serotonin release in the rat hippocampus.

The effects of the electrically evoked serotonin release were evaluated on the binding of (18)F-MPPF in the hippocampus of anesthetized rats. The specific binding of (18)F-MPPF was measured by an implanted beta-microprobe and the serotonin (5-HT) extracellular concentration was measured by microdialysis under the same conditions. Our results showed that the 10-, 20-, or 30-min electrical stimulation of the raphe nucleus elicited a significant increase in extracellular 5-HT, only detectable in the presence of a 5-HT reuptake inhibitor in the perfusate (5 microM clomipramine).

Combined positron emission tomography/computed tomography imaging of recurrent thyroid cancer.

Objective: The study goal was to evaluate the use of combined positron emission tomography/computed tomography (PET/CT) imaging for localization of recurrent disease in thyroid cancer patients.

Study Design And Setting: Eight patients with suspected recurrence of thyroid cancer on the basis of elevated serum thyroglobulin or calcitonin levels underwent combined PET/CT imaging on a prototype device. All 8 patients had previously undergone total thyroidectomy and (131)I ablation for thyroid carcinoma.

Effects of subthalamic nucleus stimulation on actual and imagined movement in Parkinson's disease : a PET study.

Background: PET studies in moderately affected Parkinson's disease (PD) patients reveal abnormal cerebral activation during motor execution and imagery, but the effects of subthalamic nucleus (STN) stimulation are not well established.

Objectives: to assess the effect of STN stimulation on cerebral activation during actual and imagined movement in patients with advanced PD.

Methods: seven severely affected PD patients treated with bilateral STN stimulation were studied with PET and H(2)(15)O.

PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow.

Cats were trained to stay in a containment box, without developing any signs of behavioural stress, while their head was maintained in a position that allowed positron emission tomography (PET) experiments to be performed. The binding potential for [(11)C]raclopride (BP(raclo)), a radioligand with good specificity for dopamine (DA) receptors of the D(2) type, was measured in the striatum and in three experimental situations: awake, anaesthetised with ketamine (50 mg kg(-1) h(-1); i.m.

The potential of the beta-Microprobe, an intracerebral radiosensitive probe, to monitor the [(18)F]MPPF binding in the rat dorsal raphe nucleus.

The aim of this study was to demonstrate the ability of a recently developed beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the beta-Microprobe.

Modeling [18 F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection.

The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2;-methoxyphenyl)-1-[2;-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired during a 160-minute session in five healthy males.

Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels.

Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas.

The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids.

Background: Several findings in humans support the hypothesis of links between n-3 polyunsaturated fatty acid (PUFA) status and psychiatric diseases.

Objective: The involvement of PUFAs in central nervous system function can be assessed with the use of dietary manipulation in animal models. We studied the effects of chronic dietary n-3 PUFA deficiency on mesocorticolimbic dopamine neurotransmission in rats.

Effect of endogenous serotonin on the binding of the 5-hT1A PET ligand 18F-MPPF in the rat hippocampus: kinetic beta measurements combined with microdialysis.

By using a combination of an original beta+-sensitive intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of 18F-MPPF [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido]ethyl]piperazine] to the serotonin-1A (5-HT1A) receptors was investigated in the hippocampus of the anaesthetized rat. Our beta-sensitive probe prototype was sensitive enough to obtain specific 18F-MPPF time-activity curves in the rodent (hippocampus/cerebellum ratio approximately 2). The serotonin neuronal release was pharmacologically enhanced using fenfluramine at three different doses (1, 2 and 10 mg/kg intravenous) multiplying by 2-15 the extracellular serotonin in the hippocampus.

Neither the density nor function of striatal dopamine transporters were influenced by chronic n-3 polyunsaturated fatty acid deficiency in rodents.

We hypothesized that the chronic dietary deficiency of n-3 polyunsaturated fatty acids (n-3 PUFAs) might affect the density and/or function of dopamine transporters (DAT), which have a major role in regulating the synaptic level of dopamine. This hypothesis was tested by investigating DAT in the striatum using three complementary methods in control and deficient rats. The density of DAT was determined by quantitative autoradiography using [(125)I]PE2I, a specific ligand of this transporter.

SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride.

Unlabelled: Our aim was to show the ability of a recently developed beta(+)-range-sensitive intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in small animals.

Methods: The potential of the device for pharmacokinetic studies was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride, a well-documented D(2) dopaminergic receptor ligand, in rat brain after intravenous injection of the labeled compound. The effects of preinjection of the unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally) on in vivo (11)C-raclopride binding were monitored by SIC.

Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals.

Olfactory receptor neurons of the nasal epithelium project via the olfactory nerve (ON) to the glomeruli of the main olfactory bulb, where they form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the olfactory bulb, and with juxtaglomerular interneurons. The glomerular layer contains one of the largest population of dopamine (DA) neurons in the brain, and DA in the olfactory bulb is found exclusively in juxtaglomerular neurons. D2 receptors, the predominant DA receptor subtype in the olfactory bulb, are found in the ON and glomerular layers, and are present on ON terminals.

Polyunsaturated fatty acids and cerebral function: focus on monoaminergic neurotransmission.

More and more reports in recent years have shown that the intake of polyunsaturated fatty acids (PUFA) constitutes an environmental factor able to act on the central nervous system (CNS) function. We recently demonstrated that the effects of PUFA on behavior can be mediated through effects on the monoaminergic neurotransmission processes. Supporting this proposal, we showed that chronic dietary deficiency in alpha-linolenic acid in rats induces abnormalities in several parameters of the mesocortical and mesolimbic dopaminergic systems.

Two-year results from the asthma self-management program: long-term impact on health care services, costs, functional status, and productivity.

Participants in a variety of health plans, clinics and employer groups were invited to participate in the Asthma Self-Management Program (ASMP), an education program designed to improve self-management skills and daily functioning in individuals with asthma. The ASMP is an 8-week classroom program that provides information on the respiratory system, trigger avoidance, use of monitoring techniques and asthma medications. After program completion, graduates were contacted at scheduled intervals to reinforce performance of behaviors that are important to asthma self-management and to collect outcomes data.

Microdialysis as a tool for in vivo study of dopamine transporter function in rat brains.

The role of dopamine as a major modulator of CNS function is well-known, and the homeostasis of dopamine is considered to be of major importance in the pathogenesis of several psychiatric and neurological diseases. Few methods are currently available for in vivo study of dopamine transporter function, which regulates extracellular levels of dopamine. Adapting the 'indicator diffusion' method applied to the microdialysis technique, we present here a suitable method for this functional investigation.

Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex.

We studied the effects of a chronic deficiency in n-3 polyunsaturated fatty acids (n-3 PUFA) on the vesicle dopaminergic compartment in the frontal cortex of rats. Electronic micrographic analysis showed that the synaptic density and the clear vesicle density were similar in deficient and control rats. However, dopaminergic immunolabeling revealed a significantly decreased number of gold-labeled vesicles in the dopaminergic presynaptic terminals of the deficient rats.

Modification of dopamine neurotransmission in the nucleus accumbens of rats deficient in n-3 polyunsaturated fatty acids.

We studied the effects of a diet chronically deficient in alpha-linolenic acid, the precursor of long-chain n-3 polyunsaturated fatty acids, on dopaminergic neurotransmission in the shell region of the nucleus accumbens of rats. In vivo microdialysis experiments showed increased basal levels of dopamine and decreased basal levels of metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in awake rats from the deficient group compared to controls. The release of dopamine under KCl stimulation was similar in both dietary groups.

Pharmacological characterization of (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)n ortropane as a selective and potent inhibitor of the neuronal dopamine transporter.

The pharmacological properties of the iodinated derivative of cocaine (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-me thylphenyl)nortropane (PE2I) were evaluated in vitro in the rat. Binding experiments on rat striatal membranes showed that PE2I selectively recognized the dopamine transporter (DAT) according to a single binding site model with high affinity (K(d) = 4 nM, B(max) = 12 pmol/mg protein). In the cortical membranes, the binding of PE2I was also selectively associated with the DAT (IC(50) for GBR 12909 = 6 nM versus more than 1000 nM for paroxetine), with similar affinity to that of the striatum.

Diagonal band stimulation increases piriform cortex neuronal excitability in vivo.

The effects of diagonal band (NDB) stimulation on the spontaneous discharge of pyramidal cells and evoked field potentials (FPs) in piriform cortex (PC) were investigated in vivo. NDB stimulation increased the spontaneous firing rate of PC cells, and increased the disynaptic excitatory (B1) and decreased the disynaptic inhibitory (P2) FP components following lateral olfactory tract (LOT) stimulation. NDB stimulation decreased the P2 component following activation of association fibers in caudal PC.

Prominent Role of n-3 Polyunsaturated Fatty Acids in Cortical Dopamine Metabolism.

In this study the effects of n-3 polyunsaturated fatty acids (PUFA) diet deficiency on dopamine metabolism were investigated in the rat frontal cortex by autoradiographic studies and microdialysis. Our results showed a 39% reduction in the vesicular monoamines transporter sites in the deficient group. The dopamine metabolites turnover after monoamine oxidase inhibition was increased in deficient rats without modification of the dopamine turnover.

[Fetal supraventricular tachyarrhythmias. Experience of a fetal cardiology referral center].

Purpose: To describe the presentation, diagnosis and treatment of fetal supraventricular tachyarrhythmias in a series of fetuses followed in a tertiary Fetal Cardiology Center.

Methods: Twenty-five fetuses with diagnosis of supraventricular tachyarrhytmia were reported from January 1989 to October 1997, among 3117 pregnant women referred for fetal cardiac evaluation.

Results: There were 17 fetuses with the diagnosis of supraventricular tachycardia (SVT) and 8 patients with atrial flutter (AF).