Biomedical subjects

F Crespi

Publications and source records attributed to F Crespi.

At least 19 recordsLinked to original sources

PubMed2006

Giant dipole resonance in the hot and thermalized 132Ce nucleus: damping of collective modes at finite temperature.

The gamma decay of the giant dipole resonance (GDR) in the 132Ce compound nucleus with temperature up to approximately 4 MeV has been measured, using the reaction 64Ni + 68Zn at E(beam) = 300, 400, and 500 MeV. The gamma and charged particles measured in coincidence with recoils are consistent with a fully equilibrated compound nucleus emission. The GDR width, obtained with the statistical model analysis, is found to increase almost linearly with temperature. This increase is rather well reproduced within a model including thermal shape fluctuations and the lifetime of the compound nucleus.

Journal Article↗

PubMed2002

Forced swimming test and fluoxetine treatment: in vivo evidence that peripheral 5-HT in rat platelet-rich plasma mirrors cerebral extracellular 5-HT levels, whilst 5-HT in isolated platelets mirrors neuronal 5-HT changes.

Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the present data show that the initial block of 5-HT reuptake is revealed by the selective increase in 5-HT levels (extracellular content) measured in PRP (not in insulated platelets, IPs) the 1st day of fluoxetine treatment. The initial action of this SSRI upon the 5-HT transporter in brain has also been confirmed by in vivo voltammetric data showing selective increase in the serotonergic signal following local injection of fluoxetine into the brain region studied. Successively, the major effect monitored is a decrease in 5-HT levels, which is more evident in IPs than in PRP. However, it is known that following 2 weeks treatment with an SSRI, 5-HT autoreceptors are desensitized and the serotonin synthesis is restored, together with the intracellular 5-HT levels. The present data showing that the levels of 5-HT in IPs tend to return to control values 12 days after the beginning of chronic fluoxetine treatment suggest that 5-HT levels in IPs (intracellular environment) mirror the influence of SSRI treatment upon the central 5-HT system. On the other hand, at day 12 of the chronic fluoxetine treatment, 5-HT content remains low in PRP. Similarly, low levels of 5-HT have been monitored in brain homogenate of rats chronically treated with fluoxetine. This would support the similarity between PRP preparation and brain homogenate as in both cases cells are disrupted by sample preparation. In conclusion this work supports the literature in proposing platelets as a peripheral model of central functions. In particular, the present data support the idea that peripheral 5-HT platelet levels can reflect the state of the central 5-HT system in conditions of depression. Furthermore, the main outcome of this study is that PRP may mirror central extracellular 5-HT levels, whilst IPs mirror neuronal 5-HT changes.

Animals↗

PubMed2001

Can voltammetry measure nitrogen monoxide (NO) and/or nitrites?

Recently, voltammetry with carbon fibre electrodes (CFE) has been implemented for real time measurement of nitrogen monoxide (NO) indicating that it is oxidised at the potential value of nitrites, approximately +700 mV. In contrast, here we show that modified CFE can monitor NO at oxidation potentials different than that of nitrites, i.e. +550 mV. Indeed, at +550 mV a significant increase of amperometric current levels was obtained when NO but not nitrites, were added to a phosphate buffer saline solution (PBS). Differential pulse voltammetry (DPV) supports these findings as two oxidation peaks were obtained when examining air preserved NO; peak 1 at +550 mV and peak 2 at +700 mV, respectively. In contrast, only peak 2 was monitored when nitrites or a solution of NO oxidised in air was added to PBS. Biological support to these in vitro data comes from the observation that the relaxation of an adrenaline-contracted aortic ring produced via addition of NO is concomitant with peak 1 at +550 mV. The relaxation is almost completed before the appearance of peak 2 at +700 mV. Furthermore, in vivo experiments performed in the striatum of rats show that the amperometric signal monitored at +550 mV is responsive to glutamatergic stimulation or inhibition of NO synthase.

2-Amino-5-phosphonovalerate↗

PubMed2001

Electrochemical evidence that lacidipine stimulates release of nitrogen monoxide in rat aorta.

Dihidropyridines (DHPs) such as amlodipine, lercanidipine and lacidipine, are compounds capable of vascular protection via their calcium antagonist activity. In addition, they present vascular dilatation function, which has been related to an anti endothelin efficacy, particularly for lacidipine. Recent works have suggested that DHPs modulate vascular relaxation via increase in the release of nitrogen monoxide (NO). Using voltammetry with selective biosensors the present experiments performed in rat aortic rings demonstrate the capability of DHPs to implement endothelial NO at 'useful' and not toxic nanomolar levels, with a maximum efficacy for lacidipine. This activity joins the already described positive effects of these compounds upon vascular functions.

Animals↗

PubMed2000

Voltammetric and functional evidence that N-methyl-D-aspartate and substance P mediate rat vascular relaxation via nitrogen monoxide release.

It is known that substance P acts as a vasodilator via activation of the enzyme nitrogen monoxide synthase (NOS) in endothelial tissue and it is suggested that N-methyl-D-aspartate (NMDA) could stimulate nitrogen monoxide (NO) release within nervous tissue. However, the data reported concern NO metabolites (nitrites, nitrates), while there is no clear evidence to date of the action of the latter compound within the aortic tissue. In this study, amperometry with specifically prepared carbon fiber electrodes has been applied to examine the effect of NMDA or substance P upon NO release. In particular, the data obtained confirm that NMDA can stimulate NO release in vivo, in the striatum of anaesthetized rats, and that substance P can stimulate NO release in rat aortic rings (ex vivo experiments). In addition, they indicate that NMDA also stimulates NO release in rat aortic rings. This original data has been confirmed by the observation of a vasorelaxant action of NMDA within noradrenaline precontracted aortic rings. Thus, these experiments provide the first direct evidence that NMDA can mediate vascular relaxation via NO release.

Animals↗

PubMed2000

Involvement of cholecystokinin within craving for cocaine: role of cholecystokinin receptor ligands.

In the brain, cholecystokinin (CCK) has been described to act as a central neurotransmitter or neuromodulator involved in functions such as food consumption, stress and anxiety. Recently, the CCK system has been involved in drug dependence phenomena and proposed to be correlated to a putative state of 'drug preferring' phenotype within free choice tests. CCK exerts its action in the CNS through at least two different G-protein coupled high affinity receptors, CCK1 and CCK2. Various selective CCK receptor agonists and antagonists have been synthesised. In particular, L-364,718 has been demonstrated to be a potent and selective CCK1 receptor antagonist, whereas L-365,260 is a potent and selective CCK2 receptor antagonist. More recently, GV150013 has been reported to be a highly selective CCK2 receptor antagonist. This paper reviews the putative role of the CCK system within drug dependence phenomena. In particular, it analyses the relationship between central CCK activity and the exhibition of spontaneous preference for drugs of abuse, such as cocaine or alcohol. The potential therapeutic role for CCK receptor antagonists is also discussed.

Animals↗

PubMed1998

The role of cholecystokinin (CCK), CCK-A or CCK-B receptor antagonists in the spontaneous preference for drugs of abuse (alcohol or cocaine) in naive rats.

A "free choice" two-bottle drinking test paradigm was implemented in naive adult male Wistar rats, resulting in a clear identification of rats drinking mainly water (water-preferring, WP rats) and rats spontaneously drinking also a consistent amount of a solution of cocaine (0.5 mg/ml water, cocaine-drinking, CD rats) or ethanol 10% v/v (ethanol-drinking, ED rats). Low, selective doses (5 micrograms/kg) of the specific cholecystokinin (CCK)-A receptor antagonist L-364,718 largely reduced the intake of ethanol 10% of ED rats only. In contrast, low, selective doses of GV-150013 (5 micrograms/kg) reduced significantly the consumption of cocaine of CD rats only. These results indicate that the CCK-A or B receptors are selectively involved in the modulation of alcohol or cocaine intake, respectively, and suggest an involvement of the CCKergic system in the drug-seeking behavior. WP rats and CD rats were then prepared for ex vivo electro-neurochemical analysis by means of differential pulse voltammetry (DPV) with micro-biosensors to monitor catechol, 5-hydroxyindole and peptidergic oxidation signals in the nucleus accumbens (nAcc). In this area, the peptidergic signal appeared to be related to the oxidation of endogenous CCK, which basal levels resulted higher in ED and CD rats than WP rats. Thus, the hypothesis that the endogenous tone of the CCK system is higher in the ED and CD rats than in the WP rats is proposed, and is supported by the observation that treatment with CCK-5 (CCK receptor agonist) selectively induced the WP rats to drink alcohol or cocaine. The selective effect of the CCK-antagonists on reducing the drug intake of ED or CD rats further supports this view, as it suggests that CCK antagonists may modify the individual sensitivity towards drugs of abuse set by the stimulating effect of high endogenous CCKergic tone over CCK-B or CCK-A receptors in spontaneous ED or CD rats, respectively. Therefore, the present data indicate that: i) Free-choice models may reveal the presence of individual sensitivity to alcohol or cocaine in naive rats; ii) the dopaminergic system is involved within the reward state, while peptidergic (CCKergic) activities modulate the drug-seeking state (craving state); iii) the CCK system could be a new target in the study of the drug dependency phenomenon. In particular, the data imply a CCK-A receptor mechanism in the regulation of individual sensitivity towards ethanol and a CCK-B receptor mechanism in the regulation of individual sensitivity towards cocaine. Thus, a potential therapeutic role for CCK-A antagonists in the treatment of ethanol abuse and for CCK-B antagonists in the treatment of cocaine abuse is proposed.

Adamantane↗

PubMed1997

Middle cerebral artery occlusion alters neurotransmitter activities in ipsilateral and contralateral rat brain regions: an ex vivo voltammetric study.

Differential pulse voltammetry with treated carbon fibre micro-electrodes has been successfully employed in in vivo analysis of neurotransmitter release and metabolism. This methodology has been now applied to ex vivo preparations (brain slices) in order to study diverse neurotransmitter activities in various brain regions ipsilateral and controlateral to a middle cerebral artery (MCA) occlusion performed in anaesthetised adult male rats. Data demonstrated that significant changes of voltammetric ascorbic acid levels related to the ischaemic state were monitored within the ipsilateral to MCA occlusion frontal cortex, striatum, nucleus accumbens and hippocampus which were the brain area studied. Furthermore, it appeared that voltammetric catecholaminergic and 5-hydroxy indolaminergic values measured within the nucleus accumbens controlateral to MCA occlusion differ significantly from the results monitored with the same technique in brain slices obtained from sham rats. In various studies, the brain regions contralateral to MCA occlusion are generally considered as control areas, however, the present data suggest that the nucleus accumbens contralateral to the MCA occlusion side is specifically affected by the ischaemic state.

Animals↗

PubMed1996

Concomitant in vivo electrophysiological and voltammetric analysis indicate that ascorbic acid is a biochemical index of early ischaemia.

A number of in vitro studies or in vivo cortical microdialysis measurements have observed that changes in the levels of ascorbic acid (AA), uric acid (UA), tryptophan (TRY), indoles and other compounds may be biochemical markers of cerebral ischaemic damages following occlusion of the rat middle cerebral artery (MCAO). The aim of the present work was to study the influence of early ischaemia upon presynaptic and postsynaptic activities in the cerebral cortex of rats. These activities have been studied by means of electrophysiological and electro-biochemical (voltammetric) measurements performed concomitantly every 5 min and applied with the same biosensor. The biosensor was inserted in the cerebral cortex of anaesthetised adult male rats which were then submitted to focal ischaemia via MCAO. Since changes in electrophysiological activity are considered marker of rise of ischaemia, the choice of simultaneous electrophysiological and electrochemical (voltammetric) analysis could allow the observation of specific biochemical(s) correlation(s) with the initial phase of ischaemia. The data obtained indicated that electrophysiological and voltammetric changes can be monitored simultaneously in the same brain region (i.e. effected by MCAO) by means of a single biosensor with an improved time resolution when compared with previous biochemical in vivo studies. In addition, a high correlation was observed between MCAO reduced functional responses of the neurons monitored by electrophysiology and increased levels of AA measured by voltammetry. This original observation suggests that AA is a biochemical marker of the very early stages of focal ischaemia and could be a useful tool for the evaluation of initial ischaemic damage.

Animals↗

PubMed1996

Carbon fibre micro-electrode and in vitro or in brain slices voltammetric measurement of ascorbate, catechol and indole oxidation signals: influence of temperature and physiological media.

Carbon fibre micro-electrodes have been used to determine the influence of temperature and physiological media on the oxidation potential value of three carboxylic acids of physiological interest such as ascorbate (AA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindolacetic acid (5HIAA). Standard calibrations at room temperature (18-20 degrees C) in phosphate buffered saline (PBS, pH 7.4), in Krebs (pH 7.4) or in artificial cerebral spinal fluid (ACSF, pH 7.4) have been compared with calibrations performed at 37 degrees C under 95% oxygen, 5% carbon dioxide. Ex vivo experiments were then performed with the electrode inserted in the striatum of rat brain slices maintained in ACSF at 37 degrees C under 95% oxygen, 5% carbon dioxide. The results obtained from both in vitro and ex vivo experimentation indicate that the oxidation potential of peak 2 (DOPAC) is highly sensitive to changes in temperature and medium. Therefore the extrapolation from in vitro electrode calibrations performed in PBS at room temperature to ex vivo (brain slices) and possibly in vivo measurements of DOPAC oxidation should be reconsidered.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Carbon fibre micro-electrodes for concomitant in vivo electrophysiological and voltammetric measurements: no reciprocal influences.

Differential pulse voltammetry and more recently cyclic voltammetry have been successfully used to monitor basal levels of endogenous chemicals by means of treated carbon fibre microbiosensors inserted in specific brain regions. In this study, feasibility of concomitant in vivo recordings of stable electrophysiological signals and basal ascorbate, catecholaminergic and indolaminergic voltammetric peaks at the same cerebral site by means of a single electrically treated carbon fibre micro electrode (microbiosensor) is presented. The results indicate that these two independent techniques can be combined in vivo at a single electrode, and that voltammetric measurements of unstimulated levels of extracellular compounds do not alter concomitant basal cell firing for a period long enough (more than 6 h) to allow pharmacological manipulations.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Melatonin, a hormone monitorable in vivo by voltammetry?

Melatonin, an indoleamine hormone synthesized in the pinealocytes, is electroactive at the surface of pre-treated carbon fibre microelectrodes (mCFE) in vitro when using differential-pulse voltammetry (DPV), at the specific oxidation potential of approximately +570 mV. In vivo DPV experiments have then been performed in melatonergic regions such as the pineal gland or the suprachiasmatic nucleus (SCH) of anaesthetized adult male rats. These experiments indicated the feasibility of simultaneous measurements of the indolaminergic peak 3, which occurred at approximately +280 mV, due mainly to the oxidation of extracellular 5-hydroxyindoleacetic acid (5HIAA), and a signal at approximately +580 mV which we called peak M. Pharmacological in vivo experiments performed in anaesthetized rats prepared for DPV analysis with the mCFE implanted into the pineal gland or the SCH indicated that intravenous or intra-cerebral injections of exogenous melatonin (5 mg kg-1 or 2 micrograms microliter-1, n = 3, respectively) were followed by a selective and significant increase of in vivo peak M. Other in vivo experiments with anaesthetized rats prepared for DPV analysis with the mCFE into the SCH showed that tryptophan [TRY, 30 mg kg-1 intravenous (i.v.), n = 3] and n-acetyl serotonin (nA-5HT, 5 mg kg-1 i.v., n = 3), both precursors of melatonin, were responsible for a transient but significant increase in the size of peak M (approximately 320% or 126% of control levels within 10 min or 20 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1993

Functional in vivo interaction between growth hormone and dopamine systems are correlated to changes in striatal somatostatin levels as detected by voltammetry.

The effects of growth hormone (GH) and somatomedin C (SmC), as well as those of apomorphine, dopamine (DA) agonist, or haloperidol (DA antagonist), upon the size of striatal voltammetric peaks 2 and 5 were investigated. Local intrastriatal injections of GH or SmC were followed by an increase in the height of both peak 2 (corresponding to the oxidation of extracellular dihydrophenylacetic acid, DOPAC, a metabolite of DA) and peak 5 (which may represent the oxidation of striatal extracellular somatostatin, SRIF). Treatment with haloperidol also increased the size of the striatal catechol peak but was responsible for a reduction of the neuropeptidergic signal. By contrast, apomorphine determined a decrease in striatal peak 2 (DOPAC) while increasing the levels of peak 5 (SRIF). The data further support the chemical identification of peak 5 at +800 mV as related to the in vivo oxidation of SRIF; in addition they indicate the presence of a functional relationship between this neuropeptide and the GH and DA systems in the striatum of anaesthetised rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Short-range differential pulse voltammetry for fast, selective analysis of basal levels of cerebral compounds in vivo.

Differential pulse voltammetry (DPV) with pretreated biosensors (carbon fibre microelectrodes (mCFE), 10-30 microns diameter) allows selective in vivo measurement of basal endogenous levels of dopamine (DA), serotonin (5-HT), their metabolites (dihydroxyphenylacetic acid, DOPAC; 5-hydroxyindoleacetic acid, 5-HIAA), and neuropeptides. We have now modified DPV in order to reduce the time of analysis from tens of seconds to 1-2 s without losing selectivity. We call this newly reported method short-range differential pulse voltammetry (SRDPV). Simply, while in DPV the complete oxidation peak is recorded, SRDPV measures only the top of each oxidation peak. For example, to monitor peak 2 which corresponds to the in vivo oxidation of extracellular DOPAC and occurs at approximately +85 +/- 10 mV, the initial (Ei) and final (Ef) potentials applied with DPV were -100 mV and +200 mV, respectively, while they were +75 mV (Ei) and +95 mV (Ef) with SRDPV. At the typical scan range of 10 mV.s-1, the effective time of measurement was 30 s for DPV and 2 s for SRDPV. A similar procedure was performed to analyze peak 3 (5-HIAA, occurring at +230 +/- 11 mV) with Ei + 50 mV and Ef + 350 mV for DPV, or +220 mV and +240 mV for SRDPV. DPV and SRDPV were compared in vitro by quantitating DOPAC and 5-HIAA in solutions of increasing concentrations (chosen on the basis of the suggested in vivo content of these two compounds). Data indicated that similar sensitivity and selectivity were obtained with both methods at all concentrations, supporting the applicability of SRDPV for in vitro studies. In vivo experiments were performed in anesthetized adult male rats prepared for voltammetry by inserting the electrically pretreated biosensor (mCFE) into the striatum. DPV measurements were performed automatically every 3-5 min and were alternated every 10-20 min with a sequence of 5-10 SRDPV scans performed every 10-30 s. Subsequent pharmacological or electrical manipulations of the two biogenic amine systems studied were monitored by alternate use of DPV and SRDPV. The data presented support the capability of SRDPV with pretreated biosensors to measure in vivo electroactive compounds with selectivity and sensitivity comparable to that of DPV, but with improved time resolution.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Isolation rearing of rats alters release of 5-hydroxytryptamine and dopamine in the frontal cortex: an in vivo electrochemical study.

The effects of rearing hooded Lister rats either in groups of seven or singly on 5-hydroxytryptamine (5-HT) and dopamine (DA) release in the frontal cortex were investigated using in vivo voltammetry together with Nafion coated carbon fibre micro-electrodes. The selective detection of basal extracellular levels of 5-HT with this technique (Peak B) was confirmed with parallel experiments using intracranial microdialysis to measure 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in vivo. The DA voltammetric signal (Peak A) was observed in vivo only following pharmacological or electrical stimulation of DA release. Enhanced efflux of cortical DA and 5-HT in response to local application of KCl and that of 5-HT following parentelar fenfluramine were selectively detected by the association: differential pulse voltammetry (DPV)-Nafion coated microbiosensors, supporting the capability of this electrochemical method to selectively monitor release of these amine neurotransmitters in vivo and in situ. The locomotor behaviour data indicated that isolation rearing resulted in augmented locomotor activity in a novel environment. In addition, the in vivo voltammetric results showed that following KCl or fenfluramine treatment cortical 5-HT release is prolonged while that of DA is increased in rats reared in isolation when compared with socially reared rats. This imbalance between extracellular levels of DA and 5-HT recorded in the frontal cortex of rats exposed to isolated housing conditions may contribute to the behavioural differences reported between isolation and group reared rats.

Animals↗

PubMed1992

In vivo selective monitoring of basal levels of cerebral dopamine using voltammetry with Nafion modified (NA-CRO) carbon fibre micro-electrodes.

The electrochemical technique of differential pulse voltammetry (DPV) with micro-biosensors has been used for a number of years to monitor in vivo and in situ changes in the extracellular concentration of cerebral ascorbic acid, as well as that of the metabolites of dopamine (DA) and serotonin (5-HT). We have recently prepared a carbon fibre micro-electrode (mCFE) which specifically pretreated and coated with Nafion (a negatively charged polymer which repels acids such as 3,4-dihydroxyphenylacetic acid (DOPAC)) allows the direct selective detection of the oxidation of DA and 5-HT in nanomolar concentration in vitro and that of extracellular basal levels of cerebral 5-HT in vivo (peak B at +240 mV). We describe here a modified version of this micro-biosensor now called NA-CRO mCFE as its active tip (30 microns in diameter) is coated with a 50/50 (v:v) mixture of Nafion and dibenzo-18-crown-6 (Aldrich). In vitro this newly reported electrode shows insensitivity to acids (e.g., DOPAC) up to 100 microns and sensitivity to 0.5-1 nM DA. In vivo, in the striatum of anaesthetised rats, a basal oxidation peak at +80 mV (peak A, on average 0.6 nA in height), which corresponds to the oxidation potential of DA in vitro, is consistently detectable with the NA-CRO mCFE (corresponding to an estimated concentration of 1.5 nM). Experiments performed in vivo in anaesthetised rats implanted in the striatum with uncoated (normal) mCFE to measure extracellular DOPAC or with NA-CRO mCFE have been performed in order to analyse the chemical nature of peak A in vivo. It is concluded that the addition of the crown-ether compound to the Nafion coat improves the sensitivity of the micro-biosensor for DA in vitro and allows the detection of its basal extracellular levels in vivo.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function.

The effects of the alpha 2-adrenoceptor antagonist idazoxan on 5-hydroxytryptamine (5-HT) neuronal firing and release have been investigated. Idazoxan, administered i.v. (10 micrograms/kg and 0.5 mg/kg) increased dorsal raphe nucleus (DRN)-5-HT neuronal firing rate in a dose-dependent fashion. At the higher dose, a voltammetric study revealed increases in extracellular 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels, there was no effect with the lower dose. Intra-raphe administration of idazoxan (1 ng) also elevated the firing rate of 5-HT neurones in the dorsal raphe, suggesting that idazoxan may produce the increase in firing by a direct effect in the DRN. However, microiontophoretic application of idazoxan did not increase the firing rate of 5-HT neurones in the DRN. Thus the increase in the firing rate of 5-HT neurones in the DRN observed with systemic and local administration of idazoxan is probably not due to a direct action of idazoxan on the 5-HT neurone. Possibly the idazoxan acted at alpha 2-adrenoceptors located on noradrenergic terminals thus stimulating noradrenaline release and consequently increased 5-HT activity. Chronic administration of idazoxan (0.8 mg/kg per h for 14 days), using osmotic mini-pumps, caused an elevation in basal firing rate and an attenuation of the inhibitory response of DRN 5-HT neurones to the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (10 micrograms/kg i.v.). This finding suggests that chronic infusion with idazoxan leads to desensitisation of the 5-HT1A somatodendritic autoreceptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1991

In vivo voltammetric detection of neuropeptides with micro carbon fiber biosensors: possible selective detection of somatostatin.

The electrochemical activity of catechol- and indoleamines, measured by differential pulse voltammetry (DPV) with specifically electrically pretreated carbon fiber microelectrodes, has been utilized to develop sensitive assays for amine neurotransmitters and metabolites. So far, four oxidation peaks have been recorded in vivo between -200 and +500 mV and are well identified. We now report that by increasing the potential sweep range to +950 mV, a further peak, called Peak 5, was detected at +800 mV in vivo in the striatum of anesthetized rats. Neuropeptides containing tyrosine, tryptophan and/or cysteine appear to be electrochemically active between +600 and +900 mV in vitro in a buffered solution at pH 7.4. The present study investigates the chemical nature of Peak 5 and the possible contribution of electroactive neuropeptides to this in vivo voltammetric signal. Experiments performed in vitro and in vivo with amino acids, neuropeptides, or bacitracin (a potent peptidase inhibitor) support the view that Peak 5 is peptidergic. Furthermore, peripheral administration of cysteamine and intrastriatal injection of specific somatostatin antisera both cause the eventual disappearance of Peak 5, suggesting that somatostatin (which oxidases in vitro at approx +800 mV), or a structurally related peptide, could be the principal component of striatal Peak 5.

Animals↗