-
[show abstract]
[hide abstract]
ABSTRACT: Although various brain regions have been shown to respond to the presentation of visual sexual stimuli (VSS), whether these regions are specifically mediating sexual arousal or whether they mediate general emotional or motivational arousal is unknown. To clarify this issue, our purpose was to map the regions where the response to VSS was related to plasma testosterone. Specific objectives were (i) to identify regions that respond differentially to VSS in untreated hypogonadal patients compared with healthy controls and (ii) to identify in hypogonadal patients the regions that respond differentially to VSS as a function of therapeutically induced increased testosterone levels.
In nine male hypogonadal patients, in the same patients under treatment, and in eight healthy males, we used Positron Emission Tomography to investigate responses of regional cerebral blood flow to VSS. Statistical Parametric Mapping was used to locate regions that demonstrated a differential response.
Regions responding differentially both in untreated patients compared with controls and in untreated patients compared with themselves under treatment were the right orbitofrontal cortex, insula and claustrum, where the activation was higher in controls than in untreated patients and where activation increased under treatment, and the left inferior frontal gyrus, that demonstrated a deactivation only in controls and in patients under treatment. That these responses appear to depend on testosterone indicates that these regions mediate sexual arousal and not only a process of general emotional or motivational arousal.
Psychoneuroendocrinology 07/2005; 30(5):461-82. · 5.81 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although hypoactive sexual desire disorder (HSDD) is a common condition and has long been hypothesized to result from malfunctions of the cerebral control mechanisms that adjust the level of sexual motivation, very little is known about the pathophysiology of this disorder. The primary objective was to identify in patients with HSDD brain regions where functional perturbations disrupt the regulation of sexual motivation. We used positron emission tomography to compare seven male patients with HSDD with eight healthy men on their regional cerebral blood flow responses to visual sexual stimuli (VSS) of graded intensity. Statistical Parametric Mapping was used to locate brain regions that demonstrated a differential activation (or deactivation) across the groups. Whereas in control subjects the medial orbitofrontal cortex showed a deactivation in response to VSS, in HSDD patients there was an abnormally maintained activity of this region, which has been implicated in the inhibitory control of motivated behavior. By contrast, the reverse pattern-activation in control subjects, deactivation or unchanged activity in patients-was found in the secondary somatosensory cortex and inferior parietal lobules, regions mediating emotional and motor imagery processes, as well as in those areas of the anterior cingulate gyrus and of the frontal lobes that are involved in premotor processes.
Psychiatry Research 11/2003; 124(2):67-86. · 2.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: Fv (vascular fraction), K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential were compared with indices generated by Logan-Patlak graphical analysis. The 5HT1A specificity for MPPF was evidenced. A Bmax of 2.9 pmol/mL and a Kd of 2.8 nmol/L were found in hippocampal regions, Kd and distribution volume in the free compartment were regionally stable, and the Logan binding potential was linearly correlated to Bmax. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols.
Journal of Cerebral Blood Flow & Metabolism 07/2002; 22(6):753-65. · 5.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels.
Neurochemical Research 05/2002; 27(4):269-75. · 2.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
The radioactivity curves measured as a function of time were reproducible and consistent with previous studies using PET imaging (ratio of striatum to cerebellum, 2.6 +/- 0.3 after 20 min). Further studies showed significant displacement of (11)C-raclopride by its stable analog. Finally, the device proved its capacity to accurately detect changes in (11)C-raclopride binding after a sudden (amphetamine) or a gradual (reserpine) modulation of endogenous dopamine levels.
These results show that the new device can monitor binding of PET ligands in anesthetized rodents in vivo, with high temporal resolution.
Journal of Nuclear Medicine 03/2002; 43(2):227-33. · 6.38 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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. These extracellular variations of extracellular serotonin resulted in dose-ranging decreases in 18F-MPPF-specific binding in the same rat. Our results showed for the first time that 18F-MPPF binding could be modulated by modifications of extracellular serotonin in the rat hippocampus. These results were confirmed by the enhancement of extracellular radioactivity collected in dialysates after the displacement of 18F-MPPF by fenfluramine. After modelization, 18F-MPPF binding could constitute an interesting radiotracer for positron emission tomography in evaluating the serotonin endogenous levels in limbic areas of the human brain.
Journal of Neurochemistry 02/2002; 80(2):278-86. · 4.06 Impact Factor
