Ricardo de Oliveira

Fuzzy Stabilization of Power Systems in a Co-Generation Scheme Subject to Random Abrupt Variations of Operating Conditions

In this brief, a new stabilizing controller for the power system of an industrial plant operating in a co-generation scheme is proposed. The main source of perturbations considered in the operating conditions are random abrupt fluctuations in the local load, corresponding to the industrial processes being turned on and/or off. These fluctuations are described as Markovian jumps in the parameters of the power system. The proposed controller follows a standard structure which combines an automatic voltage regulator with a supplementary stabilizing term. This term is obtained with a fuzzy-model-based control technique formulated in the context of linear matrix inequalities under damping and control input constraints. Simulations performed on both a single-machine infinite-bus model and on a multimachine model show the effectiveness of the proposed fuzzy control strategy in reducing the oscillations as well as in maintaining a desired operating condition

Involvement of 5-HT2 serotonergic receptors of the nucleus raphe magnus and nucleus reticularis gigantocellularis/paragigantocellularis complex neural networks in the antinociceptive phenomenon that follows the post-ictal immobility syndrome

The post-ictal immobility syndrome is followed by a significant increase in the nociceptive thresholds in animals and men. In this interesting post-ictal behavioral response, endogenous opioid peptides-mediated mechanisms, as well as cholinergic-mediated antinociceptive processes, have been suggested. However, considering that many serotonergic descending pathways have been implicated in antinociceptive reactions, the aim of the present work is to investigate the involvement of 5-HT(2)-serotonergic receptor subfamily in the post-ictal antinociception. The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the post-ictal period. Male Wistar rats were submitted to stereotaxic surgery for introduction of a guide-cannula in the rhombencephalon, aiming either the nucleus raphe magnus (NRM) or the gigantocellularis complex. In independent groups of animals, these nuclei were neurochemically lesioned with a unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL). The neuronal damage of either the NRM or nucleus reticularis gigantocellularis/paragigantocellularis complex decreased the post-ictal analgesia. Also, in other independent groups, central administration of ritanserin (5.0 microg/0.2 microL) or physiological saline into each of the reticular formation nuclei studied caused a statistically significant decrease in the TFL of seizing animals, as compared to controls, in all post-ictal periods studied. These results indicate that serotonin input-connected neurons of the pontine and medullarly reticular nuclei may be involved in the post-ictal analgesia.

The role of dorsomedial and ventrolateral columns of the periaqueductal gray matter and in situ 5‐HT2A and 5‐HT2C serotonergic receptors in post‐ictal antinociception

The periaqueductal gray matter (PAG) consists in a brainstem structure rich in 5‐hydroxytryptamine (5‐HT) inputs related to the modulation of pain. The involvement of each of the serotonergic receptor subtypes found in PAG columns, such as the dorsomedial (dmPAG) and the ventrolateral (vlPAG) columns, regarding post‐ictal antinociception have not been elucidated. The present work investigated the participation of the dmPAG and vlPAG columns in seizure‐induced antinociception. Specifically, we studied the involvement of serotonergic neurotransmission in these columns on antinociceptive responses that follow tonic‐clonic epileptic reactions induced by pentylenetetrazole (PTZ), an ionophore GABA‐mediated Cl‐ influx antagonist. Microinjections of cobalt chloride (1.0 mM CoCl2/0.2 µL) into the dmPAG and vlPAG caused an intermittent local synaptic inhibition and decreased post‐ictal antinociception that had been recorded at various time points after seizures. Pretreatments of the dmPAG or the vlPAG columns with the nonselective serotonergic receptors antagonist methysergide (5.0 µg/0.2 µL) or intramesencephalic microinjections of ketanserin (5.0 µg/0.2 µL), a serotonergic antagonist with more affinity to 5‐HT2A/2C receptors, decreased tonic‐clonic seizure‐induced antinociception. Both dmPAG and vlPAG treatment with either the 5‐HT2A receptor selective antagonist R‐96544 (10 nM/0.2 µL), or the 5‐HT2C receptors selective antagonist RS‐102221 (0.15 µg/0.2 µL) also decrease post‐ictal antinociception. These findings suggest that serotonergic neurotransmission, which recruits both 5‐HT2A and 5‐HT2C serotonergic receptors in dmPAG and vlPAG columns, plays a critical role in the elaboration of post‐ictal antinociception. Synapse, 68:16–30, 2014.

Paradoxical effect of noradrenaline-mediated neurotransmission in the antinociceptive phenomenon that accompanies tonic–clonic seizures: Role of locus coeruleus neurons and α2- and β-noradrenergic receptors

The postictal state is generally followed by antinociception. It is known that connections between the dorsal raphe nucleus, the periaqueductal gray matter, and the locus coeruleus, an important noradrenergic brainstem nucleus, are involved in the descending control of ascending nociceptive pathways. The aim of the present study was to determine whether noradrenergic mechanisms in the locus coeruleus are involved in postictal antinociception. Yohimbine (an α(2)-receptor antagonist) or propranolol (a β-receptor antagonist) was microinjected unilaterally into the locus coeruleus, followed by intraperitoneal administration of pentylenetetrazole (PTZ), a noncompetitive antagonist that blocks GABA-mediated Cl(-) influx. Although the administration of both yohimbine and propranolol to the locus coeruleus/subcoeruleus area resulted in a significant decrease in tonic or tonic-clonic seizure-induced antinociception, the effect of yohimbine restricted to the locus coeruleus was more distinct compared with that of propranolol, possibly because of the presynaptic localization of α(2)-noradrenergic receptors in locus coeruleus neurons. These effects were related to the modulation of noradrenergic activity in the locus coeruleus. Interestingly, microinjections of noradrenaline into the locus coeruleus also decrease the postictal antinociception. The present results suggest that the mechanism underlying postictal antinociception involves both α(2)- and β-noradrenergic receptors in the locus coeruleus, although the action of noradrenaline on these receptors causes a paradoxical effect, depending on the nature of the local neurotransmission.

Dorsal raphe nucleus and locus coeruleus neural networks and the elaboration of the sweet-substance-induced antinociception.

In order to investigate the effects of monoaminergic neurons of the dorsal raphe nucleus (DRN) and locus coeruleus (LC) on the elaboration and control of sweet-substance-induced antinociception, male albino Wistar rats weighing 180-200 g received sucrose solution (250 g/L) for 7-14 days as their only source of liquid. After the chronic consumption of sucrose solution, each animal was pretreated with unilateral microinjection of ibotenic acid (1.0 microg/0.2 microL) in the DRN or in the LC. The tail withdrawal latencies of the rats in the tail-flick test were measured immediately before and 7 days after this treatment. The neurochemical lesion of locus coeruleus, but not of DRN neural networks with ibotenic acid, after the chronic intake of sweetened solution, decreased the sweet-substance-induced antinociception. These results indicate the involvement of noradrenaline-containing neurons of the LC in the sucrose-induced antinociception. We also consider the possibility of DRN serotonergic neurons exerting some inhibitory effect on the LC neural networks involved with the elaboration of the sweet-substance-induced antinociception.

5-Hydroxytryptamine(1A) receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception

The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour

&NA; The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic‐like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non‐oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic‐like behaviour. The chemical stimulation of the VMH with 9 nmol of N‐methyl‐D‐aspartic acid (NMDA) elicited oriented and non‐oriented escape behaviours. The pretreatment of the dPAG with a non‐selective blocker of synaptic contacts, cobalt chloride (CoCl2), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9 nmol of NMDA, abolished the non‐oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl2 was followed by stimulation of the dPAG with 6 nmol of NMDA, no effect was observed either on the non‐oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein‐labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9 nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA‐labelled neural fibres with terminal boutons surrounding Fos‐labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic‐like behavioural responses. The current data suggest that the dPAG is the key structure that organises non‐oriented/explosive escape reactions associated with panic attack‐like behaviours. Graphical abstract The chemical stimulation of the dorsomedial division of the ventromedial hypothalamic nucleus (dmVMH) with NMDA at 9 nmol elicits panic‐like behavioural responses with increase of Fos protein in neuronal nuclei of the dorsal periaqueductal grey matter (dPAG). Fos‐immunolabelled neurons in dPAG are surrounded by dmVMH‐dPAG neuronal pathways terminal buttons. The inactivation of synaptic contacts in dPAG with CoCl2 abolishes the panic‐like behaviour elicited by dmVMH neuronal activation with 9 nmol of NMDA. Figure. No caption available. HIGHLIGHTSdmVMH neurons can trigger panic‐like escape but does not act independently.dPAG neurons mainly produce freezing and explosive escape independently.Projections from dmVMH to dPAG play an important role in the elaboration of defence.

5-Hydroxytryptamine2A/2C receptors of nucleus raphe magnus and gigantocellularis/paragigantocellularis pars α reticular nuclei modulate the unconditioned fear-induced antinociception evoked by electrical stimulation of deep layers of the superior colliculus and dorsal periaqueductal grey matter

HighlightsThe electrical stimulation of dlSC and dlPAG neurons elicits fear‐induced antinociception.Gi/PGi&agr; 5‐HT2A/2C receptors modulate fear‐induced antinociception evoked by dlSC activation.Gi/PGi&agr; 5‐HT2A/2C receptors modulate fear‐induced antinociception evoked by dlPAG activation.NRM 5‐HT2A/2C receptors modulate fear‐induced antinociception evoked by dlSC activation.NRM 5‐HT2A/2C receptors modulate fear‐induced antinociception evoked by dlPAG activation. ABSTRACT The electrical stimulation of the dorsolateral columns of the periaquedutal grey matter (dlPAG) or deep layers of the superior colliculus (dlSC) evokes defensive behaviours followed by an antinociceptive response. Monoaminergic brainstem reticular nuclei are suggested to comprise the endogenous pain modulatory system. The aim of the present work was to investigate the role played by 5‐HT2 subfamily of serotonergic receptors of the nucleus raphe magnus (NRM) and the gigantocellularis/paragigantocellularis pars &agr; reticular nuclei (Gi/PGi&agr;) in the elaboration of instinctive fear‐induced antinociception elicited by electrical stimulation of dlPAG or of dlSC. The nociceptive thresholds were measured by the tail‐flick test in Wistar rats. The 5‐HT2A/2C‐serotonergic receptors antagonist ritanserin was microinjected at different concentrations (0.05, 0.5 and 5.0 &mgr;g/0.2 &mgr;L) either in Gi/PGi&agr; or in NRM. The blockade of 5‐HT2 receptors in both Gi/PGi&agr; and NRM decreased the innate fear‐induced antinociception elicited by electrical stimulation of the dlSC or the dlPAG. These findings indicate that serotonin is involved in the hypo‐algesia induced by unconditioned fear‐induced behavioural responses and the 5‐HT2A/2C‐serotonergic receptor subfamily in neurons situated in the Gi/PGi&agr; complex and NRM are critically recruited in pain modulation during the panic‐like emotional behaviour.

Decrease in NMDA receptor-signalling activity in the anterior cingulate cortex diminishes defensive behaviour and unconditioned fear-induced antinociception elicited by GABAergic tonic inhibition impairment in the posterior hypothalamus

Acute γ-aminobutyric acid (GABA) disinhibition in the posterior hypothalamus (PH) elicits defensive reactions that are considered anxiety- and panic attack-like behaviour, and these defensive reactions are followed by antinociception. Evidence indicates that the PH connects with the medial prefrontal cortex, particularly the anterior cingulate cortex (ACC), which seems to regulate these unconditioned fear-induced defensive responses. However, few studies have shown the participation of cortical regions in the control of behavioural and antinociceptive responses organised by diencephalic structures. It has been suggested that the glutamatergic system can mediate this cortical influence, as excitatory imbalance is believed to play a role in both defensive mechanisms. Thus, the aim of the present study was to investigate the involvement of ACC glutamatergic connections via blockade of local N-methyl-D-aspartate (NMDA) receptors to elaborate panic-like defensive behaviours and unconditioned fear-induced antinociception organised by PH neurons. Wistar rats were treated with microinjections of 0.9% NaCl or LY235959 (a selective NMDA receptor antagonist) in the ACC at different concentrations (2, 4 and 8 nmol/0.2μL), followed by GABAA receptor blockade in the PH. Defensive reactions were analysed for 20min, and the nociceptive threshold was then measured at 10-min intervals for 60min. Pretreatment of the ACC with LY235959 reduced both panic-like defensive behaviour and fear-induced antinociception evoked by PH GABAergic disinhibition. Our findings suggest that ACC NMDA receptor-signalled glutamatergic inputs play a relevant role in the organisation of anxiety- and panic attack-like behaviours and in fear-induced antinociception.

Nicotinic and muscarinic cholinergic receptors are recruited by acetylcholine-mediated neurotransmission within the locus coeruleus during the organisation of post-ictal antinociception.

Post-ictal antinociception is characterised by an increase in the nociceptive threshold that accompanies tonic and tonic-clonic seizures (TCS). The locus coeruleus (LC) receives profuse cholinergic inputs from the pedunculopontine tegmental nucleus. Different concentrations (1μg, 3μg and 5μg/0.2μL) of the muscarinic cholinergic receptor antagonist atropine and the nicotinic cholinergic receptor antagonist mecamylamine were microinjected into the LC of Wistar rats to investigate the role of cholinergic mechanisms in the severity of TCS and the post-ictal antinociceptive response. Five minutes later, TCS were induced by systemic administration of pentylenetetrazole (PTZ) (64mg/kg). Seizures were recorded inside the open field apparatus for an average of 10min. Immediately after seizures, the nociceptive threshold was recorded for 130min using the tail-flick test. Pre-treatment of the LC with 1μg, 3μg and 5μg/0.2μL concentrations of both atropine and mecamylamine did not cause a significant effect on seizure severity. However, the same treatments decreased the post-ictal antinociceptive phenomenon. In addition, mecamylamine caused an earlier decrease in the post-ictal antinociception compared to atropine. These results suggest that muscarinic and mainly nicotinic cholinergic receptors of the LC are recruited to organise tonic-clonic seizure-induced antinociception.