Activation of 5-HT2C receptors in the dorsal periaqueductal gray increases antinociception in mice exposed to the elevated plus-maze

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Blockade of 5-HT2 receptors in the periaqueductal grey matter (PAG) abolishes the anxiolytic-like effect of 5-HT1A receptor antagonism in the median raphe nucleus in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bases neurofisiológicas da dependência do tabaco

A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.

Involvement of dopamine receptors in diethylpropion-induced conditioning place preference

Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N = 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 ± 39 vs 565 ± 48 s). Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg, sc) 10 min before DEP (15 mg/kg, ip) blocked DEP-induced CPP (418 ± 37 vs 389 ± 31 s) while haloperidol (0.5 mg/kg, ip), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 ± 36 vs 536 ± 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DEP

The reinstatement of amphetamine-induced place preference is long-lasting and related to decreased expression of AMPA receptors in the nucleus accumbens

A great deal of effort has been devoted to elucidating the psychopharmacology underlying addiction and relapse. Long-term neuroadaptations in glutamate transmission seem to be of great relevance for relapse to stimulant abuse. In this study, we investigated amphetamine-induced conditioned place preference during adolescence and the reinstatement of the conditioned behavior following a priming injection of the drug 1 day (adolescence), 30 days (early adulthood) and 60 days (adulthood) after the extinction test. The nucleus accumbens was dissected immediately after the reinstatement test to examine alterations in GluR1 and NR1 subunits of glutamatergic receptors. Our results showed that a priming injection of amphetamine was able to reinstate the CPP 1 and 30 days after extinction. However, it failed to reinstate the conditioned response after 60 days. GluR1 levels were decreased on days 1 and 30 but not on day 60 while NR1 levels were unaltered in the reinstatement test. Using a relapse model we found that reinstatement of amphetamine-induced conditioning place preference during adolescence is long lasting and persists through early adulthood. Decreased levels of GluR1 in the nucleus accumbens might be related to the reinstatement of amphetamine-induced conditioning place preference. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Alterações da default mode network provocadas pela ingestão de Ayahuasca investigadas por Ressonância Magnética Funcional

Ayahuasca is psychotropic beverage that has been used for ages by indigenous populations in South America, notably in the Amazon region, for religious and medicinal purposes. The tea is obtained by the decoction of leaves from the Psychotria viridis with the bark and stalk of a shrub, the Banisteriopsis caapi. The first is rich in N-N-dimethyltryptamine (DMT), which has an important and well-known hallucinogenic effect due to its agonistic action in serotonin receptors, specifically 5-HT2A. On the other hand, β-carbolines present in B. caapi, particularly harmine and harmaline, are potent monoamine oxidase inhibitors (MAOi). In addition, the tetrahydroharmine (THH), also present in B. caapi, acts as mild selective serotonin reuptake inhibitor and a weak MAOi. This unique composition induces a number of affective, sensitive, perceptual and cognitive changes in individuals under the effect of Ayahuasca. On the other hand, there is growing interest in the Default Mode Network (DMN), which has been consistently observed in functional neuroimaging studies. The key components of this network include structures in the brain midline, as the anterior medial frontal cortex, ventral medial frontal cortex, posterior cingulate cortex, precuneus, and some regions within the inferior parietal lobe and middle temporal gyrus. It has been argued that DMN participate in tasks involving self-judgments, autobiographical memory retrieval, mental simulations, thinking in perspective, meditative states, and others. In general, these tasks require an internal focus of attention, hence the conclusion that the DMN is associated with introspective mental activity. Therefore, this study aimed to evaluate by functional magnetic resonance imaging (fMRI) changes in DMN caused via the ingestion of Ayahuasca by 10 healthy subjects while submitted to two fMRI protocols: a verbal fluency task and a resting state acquisition. In general, it was observed that Ayahuasca causes a reduction in the fMRI signal in central nodes of DMN, such as the anterior cingulate cortex, the medial prefrontal cortex, the posterior cingulate cortex, precuneus and inferior parietal lobe. Furthermore, changes in connectivity patterns of the DMN were observed, especially a decrease in the functional connectivity of the precuneus. Together, these findings indicate an association between the altered state of consciousness experienced by individuals under the effect of Ayahuasca, and changes in the stream of spontaneous thoughts leading to an increased introspective mental activity

O Núcleo genuíno lateral dorsal do tálamo do sagüi (callithrix jacchus): Pprojeção retiniana, caracterização citoarquitetônica e neuroquimica da principal estação visual primária.

The thalamus plays an important role in the sensorial processing information, in this particular case, the visual information. Several neuronal groups have been characterized as conductors and processors of important sensorial information to the cerebral cortex. The lateral geniculate complex is one to them, and appears as a group very studied once it is responsible, in almost all totality, for the processing of visual information. Among the nuclei that constitute the lateral geniculate complex we highlight the dorsal lateral geniculate nucleus of the thalamus (DLG), the main thalamic relay for the visual information. This nucleus is located rostral and lateral to medial geniculate nucleus and ventral to thalamic pulvinar nucleus in most of the mammals. In the primates humans and non-humans, it presents as a laminate structure, arranged in layers, when observed in coronal sections. The objective of this work was to do a mapping of the retinal projections and a citoarchictetonic and neurochemical characterization of DLG in the marmoset (Callithrix jacchus), a New World primate. The retinal projections were traced by anterograde transport of subunit b of cholera toxin (CTb), the citoarchicteture was described by Nissl method, and to neurochemical characterization immunohistochemicals technical were used to examine the main neurotransmitters and neuroatives substances present in this neural center. In DGL of marmoset thalamus, in coronal sections labeled by Nissl method, was possible to visualize the division of this nucleus in four layers divided in two portions: magnocellular and parvocellular. The retinal projections were present being visualized fibers and terminals immunorreactives to CTb (IR-CTb) in the DLG ipsilateral and contralateral. And through the immunohistochemicals techniques was observed that DLG contain cells, fibers and/or terminals immunoreactives against neuronal nuclear protein, subunits of AMPA 15 glutamate receptors (GluR1, GluR2/3, GluR4), choline acetyltransferase, serotonin, glutamic acid decarboxylase, binding calcium proteins (calbindin, parvalbumin and calretinin), vasopressin, vasoactive intestinal polypeptide, and an astrocyte protein, glial fibrillary acidic protein.

Delimitação dos grupamentos serotoninérgicos/núcleos da rafe do mocó (kerodon rupestris): citoarquitetura e imunoistoquímica para serotonina

Serotonin or 5-hydroxytryptamine (5-HT) is a substance found in many tissues of the body, including as a neurotransmitter in the nervous system, in which may exert varied post-synaptic actions. Inside the neuro-axis, the location of 5-HT neurons is almost restricted to the raphe nuclei of the brainstem, such that 5-HT-immunoreactivity can be considered a marker of the raphe nuclei. The raphe nuclei are located in the brainstem, at or near the midline. The serotonergic groups were originally alphanumerically classified as B1 to B9 towards caudorrostral in rats and can be divided into upper and lower groups. In this study the distribution of serotonergic neurons was studied using immunohistochemistry in the brain of the rock cavy (Kerodon rupestris), a species of rodent endemic to Northeastern Brazil. The cytoarchitectonic location of serotonergic neurons was established in series of adjacent coronal and sagittal sections stained by the Nissl method and immunohistochemistry for 5-HT. Thus, we defined the raphe rostral linear, caudal linear, dorsal, median, and paramedian pontine raphe nuclei, and B9 cluster, constituting the rostral group, and the interpositus, magnus, obscure and palidus, constituting the caudal part of the group, comparable to which has been described for other mammalian species

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

TLR4 and CD14 receptors expressed in rat pineal gland trigger NFKB pathway

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Analysis of the expression of toll-like receptors 2 and 4 and cytokine production during experimental Leishmania chagasi infection

Toll-like receptors (TLRs) recognise pathogen-derived molecules and influence immunity to control parasite infections. This study aimed to evaluate the mRNA expression of TLRs 2 and 4, the expression and production of the cytokines interleukin (IL)-12, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17, IL-10 and transforming growth factor (TGF)-β and the production of nitric oxide (NO) in the spleen of mice infected with Leishmania chagasi. It also aimed to evaluate any correlations between mRNA expression TLR2 and 4 and cytokines and NO production. Infection resulted in increased TLR2-4, IL-17, TNF-α and TGF-β mRNA expression during early infection, with decreased expression during late infection correlating with parasite load. IFN-γ and IL-12 mRNA expression decreased at the peak of parasitism. IL-10 mRNA expression increased throughout the entire time period analysed. Although TGF-β, TNF-α and IL-17 were highly produced during the initial phase of infection, IFN-γ and IL-12 exhibited high production during the final phase of infection. IL-10 and NO showed increased production throughout the evaluated time period. In the acute phase of infection, there was a positive correlation between TLR2-4, TNF-α, IL-17, NO, IL-10 and TGF-β expression and parasite load. During the chronic phase of infection, there was a positive correlation between TLR2-4, TNF-α, IL-17 and TGF-β expression and parasite load. Our data suggest that infection by L. chagasi resulted in modulation of TLRs 2 and 4 and cytokines.

Physical exercise on the rat ventral prostate: Steroid hormone receptors, apoptosis and cell proliferation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Immunohistochemical detection of receptors for oestrogen and progesterone in endometrial glands and stroma during the oestrous cycle in Nelore (Bos taurus indicus) cows

The aim of the present study was to monitor endometrial distribution and concentrations of oestrogen receptors alpha (ER alpha) and progesterone receptors (PR) by immunohistochemistry in Nelore cows (Bos taurus indicus) during the oestrous cycle. Blood samples were collected for progesterone measurement and endometrial samples were taken from the uterine horn contra lateral to the corpus luteum in 16 cows at days 0 (ovulation), 5, 9, 13 and 19 of the oestrous cycle. Immunostaining evaluation for ER alpha and PR in the glandular epithelium and uterine stroma was performed by two methods: positive nuclei counting and staining intensity of the nuclei. Specific positive staining reactions for both receptors were limited to cell nuclei and they were not identified in the cytoplasm. The proportion of ER alpha positive nuclei had a temporal variation throughout the oestrous cycle in both cell types evaluated and was higher in uterine stroma than the glandular epithelium (p < 0.05). The greatest proportion of ER alpha stained nuclei was observed at oestrus and during the initial and mid luteal phase (days 5, 9 and 13) (p < 0.05) in the glandular epithelium and at days 0, 5 and 9 in the uterine stroma (p < 0.01). The proportion of PR positive nuclei remained constant throughout the entire oestrous cycle for both cell types evaluated (p > 0.05). A higher proportion of PR positive nuclei was measured in the uterine stroma compared with the glandular epithelium (p < 0.05). Intensity of staining for ER alpha and PR varied throughout the oestrous cycle (p < 0.01). There was a higher staining intensity at days 0 and 5 in the stroma for ER alpha (p < 0.01) and PR (p < 0.01) and in the glandular epithelium at days 0, 5, 9 and 13 for ER alpha (p < 0.01) and at days 0, 5 and 9 for PR (p < 0.01) when compared with the other evaluated days. These data demonstrate that ER alpha and PR expression varied throughout the oestrous cycle in Nelore cows, in general with highest concentrations at oestrus and the lowest during the luteal phase. This is similar to patterns observed in Bos taurus taurus.

The role of chemokines and chemokine receptors in eosinophil activation during inflammatory allergic reactions

Chemokines are important chemotactic cytokines that play a fundamental role in the trafficking of leukocytes to sites of inflammation. They are also potent cell-activating factors, inducing cytokine and histamine release and free radical production, a fact that makes them particularly important in the pathogenesis of allergic inflammation. The action of chemokines is regulated at the level of agonist production and processing as well as at the level of receptor expression and coupling. Therefore, an analysis of the ligands must necessarily consider receptors. Eosinophils are target cells involved in the allergic inflammatory response since they are able to release a wide variety of mediators including CC and CXC chemokines and express their receptors. These mediators could damage the airway epithelial cells and might be important to stimulate other cells inducing an amplification of the allergic response. This review focuses on recently emerging data pertaining to the importance of chemokines and chemokine receptors in promoting eosinophil activation and migration during the allergic inflammatory process. The analysis of the function of eosinophils and their chemokine receptors during allergic inflammation might be a good approach to understanding the determinants of asthma severity and to developing novel therapies.