Participation of NK1 receptors of the amygdala on the processing of different types of fear.

The amygdala, medial hypothalamus, dorsal periaqueductal gray (dPAG), superior and inferior colliculus together constitutes the encephalic aversion system which has been considered the main neural substrate for the integration of unconditioned aversive behavioral states. Within the amygdala the basolateral nucleus (BLA) is thought to act as a filter for innate and learned aversive information to higher structures, whereas the central nucleus (CeA) is considered the main output for the expression of fear reactions through projections to limbic and brainstem regions. Although neurokinin (NK) receptors are abundant in the amygdala, their role in the processing and expression of fear is yet unclear. In this study, we examined the role of SP/NK1 receptor system of the CeA and BLA on the expression of defensive responses elaborated by Wistar rats submitted to elevated plus maze (EPM) and to electrical stimulation (ES) of the dPAG. For EPM test, cannulae were implanted in the CeA and BLA for injections of substance P (SP - 10 and 100pmol/0.2µL) and spantide (SPA - 10, 100 and 500pmol/0.2µL). For ES of dPAG, aversive thresholds for freezing and escape responses as well as post-stimulation freezing (PSF) were measured in rats treated with PBS and SPA (100pmol/0.2µL) in CeA. Injections of SP into the CeA, but not the BLA, produced anxiogenic-like effects in the EPM test. SPA injected into the CeA had no effect on the exploratory behavior of rats submitted to the EPM but blocked the effects of SP. The duration of dPAG-PSF was also reduced significantly following injection of SPA in CeA but had no effect on thresholds for freezing and escape responses. The EPM gives the animal a control over its environment i.e. the option to choose or not to enter into the open arm and dPAG-PSF is thought to reflect a period when the animal evaluates the significance of dPAG-evoked aversion once the unconditioned responses of freezing and escape were elicited. The data indicate that SP may be involved in mediating responses of the animal in only certain types of aversive behavior and suggests a differential participation of the NK1 receptors in the processing of distinct types of fear in the amygdala.

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 μL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety.

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavior. Freezing also ensues after termination of dPAG stimulation (post-stimulation freezing). These defensive reaction responses are critically mediated by γ-aminobutyric acid and 5-hydroxytryptamine mechanisms in the midbrain tectum. Neurokinins (NKs) also play a role in the mediation of dPAG stimulation-evoked fear, but how NK receptors are involved in the global processing and expression of fear at the level of the midbrain tectum is yet unclear. The present study investigated the role of NK-1 receptors in unconditioned defensive behavior induced by electrical stimulation of the dPAG and IC of male Wistar rats. Spantide (100 pmol/0.2 µL), a selective NK-1 antagonist, injected into these midbrain structures had anti-aversive effects on defensive responses and distress ultrasonic vocalizations induced by stimulation of the dPAG but not of the IC. Moreover, intra-dPAG injections of spantide did not influence post-stimulation freezing or alter exploratory behavior in rats subjected to the elevated plus maze. These results suggest that NK-1 receptors are mainly involved in the mediation of defensive behavior organized in the dPAG. Dorsal periaqueductal gray-evoked post-stimulation freezing was not affected by intra-dPAG injections of spantide, suggesting that NK-1-mediated mechanisms are only involved in the output mechanisms of defensive behavior and not involved in the processing of ascending aversive information from the dPAG.

Effects of neurokinin-1 and 3-receptor antagonists on the defensive behavior induced by electrical stimulation of the dorsal periaqueductal gray.

The dorsal periaqueductal gray (dPAG) is the main output structure for the defensive response to proximal aversive stimulation. Panic-like responses, such as freezing and escape behaviors, often result when this structure is electrically stimulated. Freezing also ensues after termination of the dPAG stimulation (post-stimulation freezing (PSF)). GABA and 5-HT have been proposed as the main neuromediators of these defense reactions. Neurokinins (NKs) also play a role in the defense reaction; however, it is unclear how the distinct types of NK receptors are involved in the expression of these fear responses. This study investigated the role of NK-1 and NK-3 receptors in the unconditioned defensive behaviors induced by electrical stimulation of the dPAG of rats, with and without previous experience with contextual fear conditioning (CFC). Spantide (100 ρmol/0.2 µl) and SB 222200 (50 and 100 ρmol/0.2 µl), selective antagonists of NK-1 and NK-3 receptors, respectively, were injected into the dPAG. Injection of spantide had antiaversive effects as determined by stimulation of the dPAG in naive animals and in animals subjected previously to CFC. SB 222200 also increased these aversive thresholds but only at doses that caused a motor deficit. Moreover, neither spantide nor SB 222200 influenced the PSF. The results suggest that NK-1 receptors are mainly involved in the mediation of the defensive behaviors organized in the dPAG. Because dPAG-evoked PSF was not affected by intra-dPAG injections of either spantide or SB 222200, it is suggested that neurokinin-mediated mechanisms are not involved in the processing of ascending aversive information from the dPAG.

Withdrawal from methylphenidate increases neural reactivity of dorsal midbrain.

Ritalin (methylphenidate hydrochloride, MP) is a non-amphetamine psychostimulant and is the drug of choice to treat children and adults diagnosed with the attention deficit hyperactivity disorder (ADHD). Several studies have demonstrated that rats treated with MP during early developmental stage exhibit alterations in anxiety-related processes such as an increased response to stressful stimuli and elevated plasma levels of corticosterone. Accordingly, the present study was designed to further characterize the neural and behavioral consequences of withdrawal from MP in adult rats and its influence on the neural reactivity of the dorsal midbrain. After initial exposure to an elevated plus-maze (EPM), brainstem neural activation, elicited by exposure to EPM aversive cues, was analyzed using a Fos-protein immunolabeling technique. Additional independent groups of animals were submitted to electrical stimulation of the dorsal column (DPAG) or the startle response procedure, in order to verify the influence of withdrawal from MP on the expression of unconditioned fear induced by DPAG activation and the effects of or withdrawal from MP on motor response, respectively. Our results provide new findings about the influence of MP treatment in adult rats, showing that, after a sudden MP treatment-break, increased anxiety, associated with the neural sensitization of anxiety-related regions, ensues.

Effect of chronic intake of sweet substance on nociceptive thresholds and feeding behavior of Rattus norvegicus (Rodentia, Muridae).

The investigation of the influence of sweetened food on feeding behavior targeted to non-sucrose nutrients as well as the sensitivity to painful stimuli in isolated and grouped animals is the aim of the present work. The tail withdrawal latencies in the tail-flick test (a spinal reflex) were measured before and immediately after the treatment with tap water or sucrose (62, 125 or 250 g/l). Our findings suggest that: (a) The analgesic effect of sucrose intake depends on the concentration of sucrose solution and on the time during which the solution is consumed; (b) the most effective concentration of sucrose followed by antinociceptive effect was the one of 250 g/l in both isolated and grouped animals; (c) considering the individually caged rats, the intake of sucrose in the highest concentration (250 g/l) was the smallest as compared with the consumption of sucrose in more diluted solutions (62.5 and 125 g/l), but this higher sweetened solution was followed by antinociception; (d) animals treated with concentrated sucrose solution ate smaller quantities of pellets than animals treated with tap water; (e) tonic intake of highly concentrated sweet substance seems to be crucial for the increase of the nociceptive threshold in our model of sweet substance-induced antinociception.

[Passive microhemagglutination reaction to Treponema pallidum in the cerebrospinal fluid in the diagnosis of neurosyphilis]. / Contribuição da reação de micro-hemaglutinação passiva para o treponema pallidum (mha-tp) no líquido cefalorraqueano ao diagnóstico de neurossífilis.

A quantitative micro-hemagglutination test for antibodies to Treponema pallidum (MHA-TP) was evaluated in 25 cerebrospinal fluid (CSF) samples obtained from patients with neurosyphilis (NS group) and in 7 CSF samples of patients with reactive serologic tests for syphilis (STS+). These data were compared to treponemal and nontreponemal tests. The MHA-TP was reactive in all of the 25 NS group samples, the FTA-Abs and the complement fixation of Wassermann (CFW) were in 24 and the VDRL in only 9. In the 7 STS+ samples (STS+ group), the MHA-TP was reactive in 6, the FTA-Abs in all of them and the nontreponemal tests were nonreactive. Results analyses support conclusion the clinical diagnosis of NS must be complemented by cytoproteic dual and immunological treponemal and nontreponemal assays in CSF. The MHA-TP test was as sensitive as FTA-Abs and required less technical and interpretative skills, contributing in association to CFW to NS diagnosis.

[Cerebrospinal fluid changes in multiple myeloma. Review of the literature and report of a case]. / Alterações do liquido cefalorraqueano no mieloma multiplo. Revisão de literatura e registro de um caso.

The authors make a literature review about the meningeal involvement in MM and verified that the presence of myeloma cells in the CSF is rare. They report a case of cranial MM in which the atypical plasma cells (plasmoblasts) were present in CSF. The CSF examination was the principal finding to the diagnosis of this case; it was confirmed by IgG monoclonal "M" gamophaty present in serum, CSF and urine obtained through proteic electrophoresis profile and by necropsy that revealed mielomatous proliferation in skull base with subarachnoidal space infiltration.

Alteracoes do liquido cefalorraqueano no mieloma multiplo: revisao de literatura e registro de um caso. / Changes in the cerebrospinal fluid in multiple myeloma: review of the literature and report of a case

Os autores fazem uma revisao de literatura sobre o comprometimento do sistema nervoso central em casos de mieloma multiplo (MM) verificando que o aparecimento de celulas plasmaticas atipicas (plasmoblastos) no LCR e raro. E apresentado um caso MM tipo IgG de localizacao predominantemente nos ossos das base do cranio. O exame do LCR foi um dos principais para o diagnostico da neoplasia, cuja citomorfologia revelou exclusivamente a presenca de plasmoblastos. A confirmacao do diagnostico se fez pelo perfil eletroforetico das proteinas do soro, do LCR e da urina, que revelou uma gamopatia monoclonal "M" tipo IgG e, tambem pelos achados de necropsia que evidenciaramm proliferacao mielomatosa nos ossos da base do cranio com infiltracao do espaco subaracnoideo craniano

Determinacao da lisozima no liquido cefalorraqueano normal e patologico. / Determination of lisozymes in the normal and pathological cerebrospinal fluid

As concentracoes da LZM foram determinadas nas amostras de LCR normal e patologico; o metodo utilizado foi o turbidimetrico melhorado. A LZM foi mensuravel em todas as amostras normais; apresentou-se aumentada em 60% e 83% dos casos de meningites virais e bacterianas, respectivamente. Foram, tambem observadas elevacoes em neurocisticercose, leucemia linfoblastica aguda, mieloma multiplo e neurocriptococose, nos dois casos de neurolues, a LZM do LCR foi normal

Infeccoes graves em recem-nascidos por bacterias do trato genital. / Severe infections in newborn infants due to bacteria of genital tract

Sao descritos dois casos de meningite bacteriana causada por Streptococcus sp tipo B-hemolitico do grupo B de Lancefield em recemnascidos. Sao discutidos aspectos clinicos, diagnostico laboratorial e etiologia