Polyaniline/poly (2-acrylamido-2-methyl-1-propanesulfonic acid) modified cellulose as promising material for sensors design.

A material based on cellulose coated with polyaniline/poly (2-acrylamido-2-methyl-1-propanesulfonic acid) (Cell/PANI-PAMPSA) was synthesized in a simple way starting from cellulose fibres, aniline and using PAMPSA as dopant. The morphology, mechanical properties, thermal stability, and electrical conductivity were investigated by means of several complementary techniques. The obtained results highlight the excellent features of the Cell/PANI-PAMPSA composite with respect to the Cell/PANI one. Based on the promising performance of this material, novel device functions and wearable applications have been tested. We focused on its possible single use as: i) humidity sensors and ii) disposable biomedical sensors to provide immediate diagnostic services as close to the patient as possible for heart rate or respiration activity monitoring. To our knowledge, this is the first time that Cell/PANI-PAMPSA system has been used for such applications.

When reporting Nocardia spp is not enough. Brain abscess caused by Nocardia farcinica.

Abscesses caused by the genus Nocardia spp are relatively rare, accounting for approximately 2 % of all brain abscesses, but with a significantly higher mortality. Special stains of brain abscess material from a 60-year-old man showed Gram-positive branching bacilli and the presence of long, acid-fast branching filamentous bacilli suggesting Nocardia infection. Presented here is a case of multidisciplinary management of a patient who developed cerebral abscesses by Nocardia farcinica, confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), that was susceptible to trimethoprim/sulfamethoxazole, linezolid, imipenem and not susceptible to minocycline. This case highlights the importance of performing subtyping and antimicrobial testing in order to improve clinical and treatment outcomes due to patterns of antibiotics resistance among Nocardia species.

Selective activation of 5-HT(2C) receptors stimulates GABA-ergic function in the rat substantia nigra pars reticulata: a combined in vivo electrophysiological and neurochemical study.

In vivo electrophysiology and microdialysis were used to investigate the physiological role of 5-HT(2C) receptors in the control of substantia nigra pars reticulata (SNr) function. Extracellular single-unit recordings were performed from putative GABA-containing neurons in the SNr of anesthetized rats, and local GABA release was studied by in vivo microdialysis in the SNr of awake freely-moving rats. Systemic administration of the selective 5-HT(2C) receptor agonist (S)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C(4)H(4)O(4) (RO 60-0175) caused a dose-dependent excitation of about 30% of the SNr neurons recorded. However, the remaining neurons were either inhibited or unaffected by systemic RO 60-0175, in similar proportion. Local application of RO 60-0175 by microiontophoresis caused excitation in the majority of SNr neurons tested (48%), whereas a group of neurons was inhibited (16%) or unaffected (36%). Both the excitatory and the inhibitory effects of systemic and microiontophoretic RO 60-0175 were completely prevented by pretreatment with SB 243213 [5-methyl-1-({2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl}carbamoyl)-6-trifluoromethylindoline], a selective and potent 5-HT(2C) receptor antagonist. Consistent with these electrophysiological data, both systemic and intranigral administration of RO 60-0175 and m-chlorophenylpiperazine (mCPP), a non-selective 5-HT(2C) agonist, markedly increased extracellular GABA levels in the SNr. The stimulatory effect of systemic and local RO 60-0175 on GABA release was completely prevented by systemic administration of SB 243213, whereas local application of SB 243213 into the SNr only partially blocked RO 60-0175-induced GABA release. It is concluded that selective activation of 5-HT(2C) receptors stimulates GABA-ergic function in the SNr, and the clinical relevance of these data is discussed.

Serotonin/dopamine interaction--focus on 5-HT2C receptor, a new target of psychotropic drugs.

Several hypotheses regarding physiopathology of major psychiatric diseases exist. Attention has been focused on cerebral monoaminergic systems, the dysfunction of which is thought to underlie various aspects of their symptomatology. There are reports describing the involvement of serotonergic and dopaminergic systems in the mechanism of action of psychotropic drugs. This article reviews current knowledge on interaction between 5-hydroxytryptamine (5-HT), acting at 5-HT2C receptors in the central dopamine (DA) systems. Since 90s, a growing body of behavioural, neurochemical and electrophysiological evidence from animal studies have demonstrated a clear role for 5-HT2C receptors in modulation of activity of dopamine neurones. This evidence has led to the suggestion that drugs acting on 5-HT2C receptors have potential as novel antipsychotic and antidepressant agents and may also be used in the treatment of other neuropsychiatric disorders such as Parkinson's disease and psychoactive substance abuse.

Role of 5-HT(2C) receptors in the control of central dopamine function.

Substantial evidence suggests that the functional status of the mesocorticolimbic dopamine (DA) system originating in the ventral tegmental area is under a phasic and tonic inhibitory control by the 5-HT system that acts by stimulating 5-HT(2C) receptor subtypes. Indeed, electrophysiological and biochemical data demonstrate that 5-HT(2C) receptor agonists decrease, whereas 5-HT(2C) receptor antagonists enhance, mesocorticolimbic DA function. However, 5-HT(2C) receptors do not appear to play a relevant role in the control of the nigrostriatal DA system originating in the substantia nigra pars compacta. In this article, the role of 5-HT(2C) receptors in the control of brain DA function will be reviewed, and the search for new therapies for neuropsychiatric disorders, such as depression, schizophrenia and drug addiction, based on these findings will be discussed.

m-Chlorophenylpiperazine excites non-dopaminergic neurons in the rat substantia nigra and ventral tegmental area by activating serotonin-2C receptors.

In vivo electrophysiological techniques were used to study the effect of m-chlorophenylpiperazine, a non-selective serotonin-2C receptor agonist, on the activity of non-dopaminergic neurons in the substantia nigra pars reticulata and the ventral tegmental area of anesthetized rats. Intravenous administration of m-chlorophenylpiperazine (5-320 microg/kg) caused a dose-dependent increase in the basal firing rate of a subpopulation of nigral neurons which do not respond to a footpinch stimulus [P(0) neurons], whereas it did not affect the activity of neurons which are responsive to the footpinch [P(+) neurons]. However, m-chlorophenylpiperazine (5-320 microg/kg) excited all non-dopaminergic neurons sampled in the ventral tegmental area. Moreover, microiontophoretic application of m-chlorophenylpiperazine (10-40 nA) caused an excitation of P(0) nigral and ventral tegmental area neurons. Pretreatment with the selective serotonin-2C receptor antagonist SB 242084 (200 microg/kg, i.v.) completely blocked the excitatory effect of i.v. m-chlorophenylpiperazine (5-320 microg/kg), both in the substantia nigra pars reticulata and in the ventral tegmental area. It is concluded that stimulation of serotonin-2C receptors by m-chlorophenylpiperazine activates non-dopaminergic (presumably GABA-containing) neurons in the substantia nigra pars reticulata and ventral tegmental area.

Neurochemical and electrophysiological evidence that 5-HT4 receptors exert a state-dependent facilitatory control in vivo on nigrostriatal, but not mesoaccumbal, dopaminergic function.

In this study we investigated, using in vivo microdialysis and single unit recordings, the role of serotonin4 (5-HT4) receptors in the control of nigrostriatal and mesoaccumbal dopaminergic (DA) pathway activity. In freely moving rats, the 5-HT4 antagonist GR 125487 (1 mg/kg, i.p.), without effect on its own, significantly reduced the enhancement of striatal DA outflow induced by 0.01 (-35%) and 0.1 (-66%), but not 1 mg/kg, s.c. haloperidol (HAL). Intrastriatal infusion of GR 125487 (1 microM) had no influence on basal DA outflow, but attenuated (-49%) the effect of 0.01 mg/kg HAL. Systemic administration of GR 125487 modified neither basal nor 0.01 mg/kg HAL-stimulated accumbal DA outflow. In halothane-anaesthetized rats, 1 or 10 mg/kg GR 125487, without effect by itself, failed to modify the changes in accumbal and striatal DA outflow elicited by electrical stimulation (300 microA, 1 ms, 20 Hz, 15 min) of the dorsal raphe nucleus. Finally, GR 125487 (444 microg/kg, i.v.), whilst not affecting basal firing of DA neurons within either the substantia nigra or the ventral tegmental area, reduced HAL-stimulated (1--300 microg/kg, i.v.) impulse flow of nigrostriatal DA neurons only. These results indicate that 5-HT4 receptors exert a facilitatory control on both striatal DA release and nigral DA neuron impulse flow only when nigrostriatal DA transmission is under activated conditions. Furthermore, they indicate that the striatum constitutes a major site for the expression of the control exerted by 5-HT4 receptors on DA release. In contrast, 5-HT4 receptors have no influence on mesoaccumbal DA activity in either basal or activated conditions.

Acute administration of amitriptyline and mianserin increases dopamine release in the rat nucleus accumbens: possible involvement of serotonin2C receptors.

Previous studies of conventional tricyclic and non-tricyclic antidepressants have suggested that a number of these drugs display considerable pharmacological activity at 5-HT2C receptors in the brain. There is evidence that 5-HT2C receptors are involved in the control of the activity of the central dopaminergic system. Therefore, the effects of amitriptyline (5 mg/kg and 10 mg/kg i.p.) and of the atypical antidepressant mianserin (2.5 mg/kg and 5 mg/kg i.p.) were studied on the extracellular concentration of dopamine (DA) in the nucleus accumbens of chloral hydrate-anesthetized rats, using intracerebral microdialysis. Amitriptyline and mianserin significantly increased DA release (+31.1 +/- 7.9% and +33.6 +/- 4.3%, respectively) at the higher doses. In addition, lower doses of mianserin (2.5 mg/kg i.p.) and amitriptyline (5 mg/kg i.p.) blocked the inhibitory action of RO 60-0175 (1 mg/kg i.p.), a selective 5-HT2C receptor agonist, on DA release. The effect of RO 60-0175 (1 mg/kg i.p.) was completely blocked by SB 242084 (2.5 mg/kg i.p.), a selective and powerful 5-HT2C receptor antagonist. Taken together, these data indicate that amitriptyline and mianserin increase DA release in the nucleus accumbens by blocking 5-HT2C receptors.

Biochemical and electrophysiological evidence that RO 60-0175 inhibits mesolimbic dopaminergic function through serotonin(2C) receptors.

In vivo microdialysis and electrophysiological techniques were used to elucidate the role of the 5-HT(2) receptor family on the control of mesolimbic dopaminergic system exerted by serotonin (5-HT). Administration of RO 60-0175 (1 mg/kg, i.p.), a selective 5-HT(2C) receptor agonist, significantly decreased dopamine (DA) release by 26+/-4% (below baseline) 60 min after injection. Moreover, RO 60-0175 (80-320 microg/kg, i.v.) dose-dependently decreased the basal firing rate of DA neurons in the ventral tegmental area (VTA), reaching its maximal inhibitory effect (53.9+/-15%, below baseline) after the dose of 320 microg/kg. The selective 5-HT(2C) receptor antagonist SB 242084 completely blocked the inhibitory action of RO 60-0175 on accumbal DA release and on the firing rate of VTA DA cells. On the contrary, both (+/-)-DOI, a mixed 5-HT(2A/2C) receptor agonist, and the selective 5-HT(2B) agonist BW 723C86, did not affect either DA release in the nucleus accumbens or the firing rate of VTA DA cells. Taken together, these data confirm that central 5-HT system exerts an inhibitory control on the mesolimbic DA system and that 5-HT(2C) receptors are involved in this effect.

Effect of acute administration of hypericum perforatum-CO2 extract on dopamine and serotonin release in the rat central nervous system.

The hydromethanolic extract of Hypericum perforatum has been shown to be an effective antidepressant, although its mechanism of action is still unclear. In this study, in vivo microdialysis was used to investigate the effects of Hypericum perforatum-CO2 extract on dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) release in various areas of brain. Administration of Hypericum perforatum extract (1 mg/kg, p.o.) caused a slight, but significant increase of DA outflow both in the nucleus accumbens and the striatum. The maximal increase of DA efflux (+19.22+/-1.93%, relative to the control group) in the nucleus accumbens occurred 100 min after administration of Hypericum perforatum. In the striatum, the extract maximally enhanced DA outflow (+24.83+/-7.49 %, relative to the control group) 80 min after administration. Extraneuronal DOPAC levels were not significantly affected by Hypericum perforatum treatment. Moreover, Hypericum perforatum (1 mg/kg, p.o.) did not produce any significant effect on either 5-HT or 5-HIAA efflux in the ventral hippocampus. This study shows for the first time that Hypericum perforatum extract is capable of increasing in vivo DA release.

Preferential modulation of mesolimbic vs. nigrostriatal dopaminergic function by serotonin(2C/2B) receptor agonists: a combined in vivo electrophysiological and microdialysis study.

Electrophysiological and in vivo microdialysis were used to investigate and compare the effect of tonic activation of serotonin(2C/2B) (5-HT(2C/2B)) receptors on nigrostriatal and mesolimbic dopaminergic (DA) function. Thus, extracellular single unit recordings of neurochemically-identified DA neurons in the SNc and the VTA, as well as simultaneous monitoring of striatal and accumbal DA release were performed following the administration of the unselective 5-HT(2C/2B) agonists, mCPP (m-chlorophenylpiperazine) and MK 212 [6-chloro-2-(1-piperazinyl)piperazine]. Both mCPP (5-320 microg/kg i. v.) and MK 212 (5-320 microg/kg i.v.) dose-dependently decreased the firing rate of VTA DA neurons. The maximal effect was reached at the cumulative dose of 320 microg/kg mCPP and MK 212, which caused a decrease of 42.6 +/- 12.8% and 56.4 +/- 12.6%, respectively. In addition, the total number of events in bursts and the number of bursts of VTA DA cells were significantly reduced by both mCPP and MK 212. On the other hand, mCPP (5-320 microg/kg i.v.) and MK 212 (5-320 microg/kg i.v.) induced a slight decrease in the basal firing rate, but not in bursting activity of SNc DA neurons. Consistent with electrophysiological data, dialysate DA levels in the nucleus accumbens decreased significantly, reaching the maximum of 26.6 +/- 9.6% below baseline levels 120 min after mCPP (1 mg/kg i.p.) administration, and of 25.2 +/- 5.5% 140 min after MK 212 (1 mg/kg i. p.) injection. DA outflow in the striatum was unaffected by both drugs. The inhibitory effect of both mCPP and MK 212 on VTA DA cell activity was blocked completely by pretreatment with the selective 5-HT(2C) antagonist SB 242084 ¿6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbamoyl] indoline¿ (200 microg/kg), given intravenously 10 min before the first injection of the 5-HT(2C/2B) agonists. SB 242084 (2. 5 mg/kg i.p.) antagonized also the decrease in DA release induced by mCPP and MK 212 in the nucleus accumbens. Taken together, these data indicate that mCPP and MK 212 selectively inhibit mesolimbic dopaminergic function by acting on 5-HT(2C) receptors. Therefore, selective 5-HT(2C) receptor agonists might be useful in clinical conditions where it is necessary to reduce the mesolimbic dopaminergic activity without affecting the nigrostriatal function.

SB 242084, a selective serotonin2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system.

Electrophysiological techniques and in vivo microdialysis were used to investigate the effect of SB 242084, a potent and selective 5-HT2C receptor antagonist in the control of nigro-striatal and mesolimbic dopaminergic function. Thus, extracellular single unit recordings were performed from neurochemically-identified dopamine (DA) neurons in the substantia nigra, pars compacta (SNc) and the ventral tegmental area (VTA), as well as monitoring of striatal and accumbal basal DA release in anesthetized rats following the administration of SB 242084 and RO 60-0175. Administration of SB 242084 (160-640 microg/kg, i.v.) caused a dose-dependent increase in the basal firing rate of VTA DA neurons, reaching its maximum (27.8+/-6%, above baseline) after 640 microg/kg. Moreover, bursting activity was significantly enhanced by SB 242084 in the VTA. On the other hand, SB 242084 (160-640 microg/kg, i.v.) did not cause any significant change in the basal firing rate and bursting activity of DA neurons in the SNc. Injection of the 5-HT2C receptor agonist RO 60-0175 (80-320% microg/kg, i.v.) dose-dependently decreased the basal firing of DA neurons in the VTA but not in the SNc. RO 60-0175 exerted its maximal inhibitory effect (53.9+/-15.1%, below baseline) in the VTA at the dose of 320 microg/kg. Basal DA release (34.8+/-9%, above baseline) and dihydroxyphenylacetic acid (DOPAC) efflux (19.7+/-7%, above baseline) were significantly enhanced in the nucleus accumbens following the intraperitoneal administration of 10 mg/kg SB 242084. Intraperitoneal injection of 5 mg/kg SB 242084 significantly increased DA release (16.4+/-6%, above baseline) in the nucleus accumbens, but did not affect DOPAC efflux. In the striatum, SB 242084 (5 and 10 mg/kg, i.p.) only slightly increased DA release above baseline (3.5+/-4 and 11.2+/-6%, respectively), without affecting DOPAC efflux in this area. However, the effect of SB 242084 in the striatum was rendered more evident by the fact that injection of the vehicle used to dissolve the drug in a group of control rats, significantly reduced basal DA output by 19.6+/-7%. Stimulation of 5-HT2C receptors by RO 60-0175 (1 mg/kg, i.p.) significantly decreased DA release in the nucleus accumbens by 26.1+/-4% (below baseline) 60 min after injection. On the other hand, RO 60-0175 (1 mg/kg, i.p.) did not cause any significant change of DA release in the striatum. However, DOPAC efflux was reduced by RO 60-0175 (1 mg/kg, i.p.) both in the striatum and the nucleus accumbens. Taken together, these data indicate that the central 5-HT system exerts a tonic and phasic inhibitory control on mesolimbic DA neuron activity and that 5-HT2C receptor subtypes are involved in this effect. Moreover, these findings might open new possibilities for the employment of 5-HT2C receptor antagonists in the treatment of neuropsychiatric disorders related to a hypofunction of central DA neurons.

Decreased chaos of midbrain dopaminergic neurons after serotonin denervation.

Neuropharmacological investigations aimed at understanding the electrophysiological correlates between drug effect and action potential trains have usually been carried out with the analysis of firing rate and bursting activity. In this study, a selective alteration of neural circuits providing inputs to ventral tegmental area dopaminergic neurons has been produced, and the corresponding electrophysiological correlates have been investigated by nonlinear dynamical analysis. The nonlinear prediction method combined with Gaussian-scaled surrogate data has been used to show the chaotic structure in the time-series corresponding to the electrical activity of ventral tegmental area dopaminergic neurons, extracellularly recorded in vivo. A decrease in chaos of ventral tegmental area dopaminergic neurons was found in a group of rats lesioned with 5,7-dihydroxytryptamine, a neurotoxin which selectively destroys serotonergic terminals. The chaos content of ventral tegmental area dopaminergic neurons in the control group and the decrease of chaos in the lesioned group cannot be explained in terms of standard characteristics of neuronal activity (firing rate, bursting activity). Moreover, in the control group a positive correlation has been found between the density-power-spectrum of the interspike intervals and the chaos content measured by nonlinear prediction S score; this relation was lost in the lesioned group. It is concluded that the impaired serotonergic tone induced by 5,7-dihydroxytryptamine reduces the chaotic behaviour of the dopaminergic cell firing pattern, while retaining many standard interspike interval characteristics. The functional role of this behaviour in a neuronal coding problem context and the implications for the pathophysiology of some mental disorders are discussed.

Reduced chaos of interspike interval of midbrain dopaminergic neurons in aged rats.

In this study, the nonlinear prediction method combined with Gaussian-scaled surrogate data was used to quantify, as a first goal, the chaotic behavior of the interspike interval of ventral tegmental area dopaminergic neurons, extracellularly recorded in vivo, in anesthetized rats. The second goal was to determine the differences in chaotic content as a function of age. Comparisons were made among three different groups of rats: young (two to four weeks of age), adult (three to four months of age) and aged (16-19 months of age). It has been found that the degree of complexity of action potential trains is reduced with aging. The chaotic content of ventral tegmental area dopamine neurons within each group and the decrease of chaos with aging cannot be explained in terms of standard characteristics of neuronal activity (firing rate, bursting activity). These data can be rationalized in the light of recent findings on the role of deterministic chaos in the functional behavior of complex biological systems, and suggests that nonlinear analysis may provide an additional method in characterizing neuronal activity.

Selective blockade of serotonin-2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study.

Electrophysiological techniques and in vivo microdialysis were used to investigate the relative contribution of central serotonin-2C/2B and serotonin-2A receptor subtypes in the control of mesolimbic and nigrostriatal dopaminergic function. Thus, extracellular single-unit recordings were performed from neurochemically identified dopamine neurons in the ventral tegmental area and the substantia nigra pars compacta, as well as simultaneous monitoring of accumbal and striatal basal dopamine release in anesthetized rats following the administration of serotonin-2C/2B (SB 206553), serotonin-2A (SR 46349B) or serotonin-2A/2B/2C (ritanserin) antagonists. Administration of SB 206553 (40-160 microg/kg, i.v.) caused a dose-dependent increase in the basal firing rate of ventral tegmental area and nigral dopamine neurons, reaching its maximum (45.2 and 28.5%, respectively) following 160 microg/kg. Moreover, burst activity was significantly enhanced by SB 206553 in the ventral tegmental area only. In contrast, injection of SR 46349B (40-160 microg/kg, i.v.), and ritanserin (40-160 microg/kg, i.v.) did not cause any significant change in the basal activity of these neurons. Basal dopamine release was significantly enhanced in both the nucleus accumbens (42%) and the striatum (33%) following the intraperitoneal administration of 5 mg/kg SB 206553. In contrast, SR 46349B (0.5 mg/kg, s.c.) and ritanserin (0.63 mg/kg, i.p.) failed to affect basal dopamine output in both regions. Taken together, these data indicate that the central serotonergic system exerts a tonic inhibitory control of mesolimbic and nigrostriatal dopaminergic pathway activity and that the serotonin-2C/2B receptor subtypes are involved in this effect. Moreover, these findings might open new possibilities for the employment of serotonin-2C/2B receptor antagonists in the treatment of neuropsychiatric disorders related to a hypofunction of central dopaminergic neurons.

Effects of acute and repeated administration of amisulpride, a dopamine D2/D3 receptor antagonist, on the electrical activity of midbrain dopaminergic neurons.

Electrophysiological techniques were used to study the effects of amisulpride, a D2/D3 dopamine receptor blocker, on the activity of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Administration of single bolus doses of amisulpride (8-32 mg/kg i.v.) induced a dose-dependent increase in the basal activity of dopaminergic neurons, in both the SNc and the VTA. The effect of amisulpride was more evident in the VTA, where it elicited a maximal excitation of 38.5 +/- 12%, whereas in the SNc it caused a peak excitation of only 22.1 +/- 9.8%. Amisulpride also increased the bursting activity of dopaminergic neurons in the VTA but not in the SNc. Microiontophoretic application of amisulpride (10-40 nA) into the SNc and the VTA caused an increase in the basal firing rate of the majority of dopaminergic neurons sampled. The excitation induced by 40 nA amisulpride was more marked in the VTA (36.1 +/- 21%) than in the SNc (25.0 +/- 18%). Moreover, microiontophoretic amisulpride (40 nA) increased the bursting activity of dopaminergic neurons in the VTA only. Repeated administration of amisulpride (20 and 50 mg/kg i.p.) for 21 consecutive days produced a significant decrease in the number of spontaneously active dopaminergic neurons in the VTA but not in the SNc. Repeated admistration of haloperidol (0.5 mg/kg i.p. ) decreased the number of dopaminergic cells both in the SNc and the VTA. The effect of repeated admistration of amisulpride on the activity of VTA dopaminergic neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. Taken together, these data confirm previous findings indicating that low doses of amisulpride preferentially increase dopaminergic transmission in the mesolimbic system. Moreover, results obtained from long-term experiments are consistent with clinical data indicating that amisulpride given at high doses is an effective antipsychotic agent, associated with a low incidence of extrapyramidal side effects.

Selective serotonin reuptake inhibitors reduce the spontaneous activity of dopaminergic neurons in the ventral tegmental area.

Electrophysiological techniques were used to study the effects of paroxetine, sertraline, and fluvoxamine on the basal activity of dopaminergic neurons in the ventral tegmental area (VTA) of rats. Acute i.v. administrations of paroxetine (20-1280 microg/kg), sertraline (20-1280 microg/kg), and fluvoxamine (20-1280 microg/ kg) caused a slight but significant reduction in the firing rate of the VTA dopaminergic cells studied. Paroxetine produced a maximal inhibitory effect of 10 +/- 11% at the cumulative dose of 160 microg/kg. Sertraline induced a dose-related inhibition of VTA dopaminergic neurons, which reached its maximum (10 +/- 7%) at the cumulative dose of 1280 microg/kg. The effect of fluvoxamine on the basal firing rate of VTA dopaminergic neurons was more pronounced as compared to that of paroxetine and sertraline, in that it produced a maximal inhibition of 17 +/- 12% at the cumulative dose of 1280 microg/kg. Acute i.v. injections of paroxetine (20-1280 microg/kg), sertraline (20-1280 microg/kg), and fluvoxamine (20-5120 microg/kg) caused a dose-dependent decrease in the basal firing rate of serotonergic neurons in the dorsal raphe nucleus (DRN). Paroxetine and sertraline stopped the spontaneous firing of serotonergic neurons at the cumulative dose of 1280 microg/kg, whereas fluvoxamine reached the same effect only at the cumulative dose of 5120 microg/kg. Pretreatment with the 5-HTA1A receptor antagonist tertatolol (1 mg/kg, i.v.) reduced the inhibitory effects of paroxetine, fluvoxamine, and sertraline on the basal activity of serotonergic neurons in the DRN. Administration of tertatolol induced a 15-fold increase in the ED50 for fluvoxamine. The antagonistic effect of tertatolol was much less evident in blocking the inhibitory action exerted by paroxetine and sertraline on the activity of serotonergic neurons. Pretreatment with tertatolol (1 mg/kg, i.v.) potentiated the inhibitory effect of fluvoxamine on the basal activity of VTA dopaminergic neurons. Tertatolol did not affect the inhibitory action exerted by paroxetine and sertraline on these neurons. It is concluded that inhibition of the basal firing rate of dopaminergic neurons in the VTA is a common characteristic of selective serotonin reuptake inhibitors (SSRIs). The effects of SSRIs on VTA dopaminergic cell activity might be relevant for their therapeutic action and may explain the origin of the reported cases of akathisia.

Selective blockade of serotonin2C/2B receptors enhances dopamine release in the rat nucleus accumbens.

The effects of mesulergine (100 and 200 microg/kg s.c.), SB 206553 (1 and 2.5 mg/kg i.p.), RP 62203 (2.5 and 4 mg/kg i.p.) and ritanserin (630 microg/kg i.p.) were studied on the extracellular concentration of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens of chloral hydrate-anesthetized rats, using intracerebral microdialysis. Mesulergine, a non selective serotonin2C/2B/2A (5-HT2C/2B/2A) receptor antagonist, significantly increased DA release, which reached a peak level (+ 20%) 60 min after drug injection and slowly returned back to baseline values. Mesulergine also caused a dose-dependent increase in DOPAC outflow. Pretreatment with mesulergine (200 microg/kg) did not change the inhibition of DA release induced by apomorphine (100 microg/kg), whereas it prevented the reduction of DOPAC outflow induced by apomorphine (100 microg/kg). Administration of SB 206553, a selective blocker of 5-HT2C/2B receptors, dose-dependently increased DA outflow. The dose of 2.5 mg/kg SB 206553 caused a linear increase of DA output which reached a peak (+75%) 40 min after injection, while 1 mg/kg induced a more gradual increase of DA release which peaked (+54%) 60 min after administration of the drug. Treatment with RP 62203, a selective 5-HT2A receptor antagonist, did not produce any significant effect on DA outflow. Administration of ritanserin, a mixed 5-HT2A/2C receptor antagonist, did not cause any significant change of DA and DOPAC outflow. Taken together, these data indicate that selective blockade of 5-HT2/2B receptor subtypes increases DA release in the rat nucleus accumbens.

Methods for the determination of nitrite by high-performance liquid chromatography with electrochemical detection.

A review on the use of high-performance liquid chromatography coupled with electrochemical detection (HPLC-ED) for the measurement of nitrite (NO2-) and nitrate (NO3-) is presented. HPLC-ED has been used for the determination of NO2- and NO3- in food, biological and environmental samples. Analysis of the current literature indicates that the measurement of NO2- and NO3- by the HPLC-ED procedure is more sensitive, selective and faster than methods based on UV absorption, photometry, fluorometry or chemiluminescence.